***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Increasing evidence suggests an important role of carbohydrate quality in the development of type 2 diabetes . OBJECTIVE Our objective was to prospect ively examine the association between glycemic index , glycemic load , and dietary fiber and the risk of type 2 diabetes in a large cohort of young women . DESIGN In 1991 , 91249 women completed a semiquantitative food-frequency question naire that assessed dietary intake .  The women were followed for 8 y for the development of incident type 2 diabetes , and dietary information was up date d in 1995 . RESULTS We identified 741 incident cases of confirmed type 2 diabetes during 8 y ( 716 300 person-years ) of follow-up . After adjustment for age , body mass index , family history of diabetes , and other potential confounders , glycemic index was significantly associated with an increased risk of diabetes ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 1.15 , 1.07 , 1.27 , and 1.59 ; 95 % CI : 1.21 , 2.10 ; P for trend = 0.001 ) . Conversely , cereal fiber intake was associated with a decreased risk of diabetes ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 0.85 , 0.87 , 0.82 , and 0.64 ; 95 % CI : 0.48 , 0.86 ; P for trend = 0.004 ) . Glycemic load was not significantly associated with risk in the overall cohort ( multivariate relative risks for quintiles 1 - 5 , respectively : 1 , 1.31 , 1.20 , 1.14 , and 1.33 ; 95 % CI : 0.92 , 1.91 ; P for trend = 0.21 ) . CONCLUSIONS A diet high in rapidly absorbed carbohydrates and low in cereal fiber is associated with an increased risk of type 2 diabetes Previous studies suggest that a low-glycaemic index ( LGI ) diet may improve insulin sensitivity ( IS ) . As IS has been shown to decrease during refeeding , we hypothesised that an LGI- v. high-GI ( HGI ) diet might have favourable effects during this phase . In a controlled nutritional intervention study , sixteen healthy men ( aged 26·8 ( SD 4·1 ) years , BMI 23·0 ( SD 1·7 ) kg/m2 ) followed 1 week of overfeeding , 3 weeks of energy restriction and of 2 weeks refeeding at ^50 % energy requirement ( 50 % carbohydrates , 35 % fat and 15 % protein ) . During refeeding , subjects were divided into two matched groups receiving either high-fibre LGI or lower-fibre HGI foods ( GI 40 v. 74 , fibre intake 65 ( SD 6 ) v. 27 ( SD 4 ) g/d ) . Body weight was equally regained in both groups with refeeding ( mean regain 70·5 ( SD 28·0)% of loss ) . IS was improved by energy restriction and decreased with refeeding . The decreases in IS were greater in the HGI than in the LGIgroup ( group £ time interactions for insulin , homeostasis model assessment of insulin resistance ( HOMAIR ) , Matsuda IS index (MatsudaISI);all P,0·05 ) . Mean interstitial glucose profiles during the day were also higher in the HGI group ( DAUCHGI-LGI of continuous interstitial glucose monitoring : 6·6 mmol/l per 14 h , P¼0·04 ) . At the end of refeeding , parameters of IS did not differ from baseline values in either diet group ( adiponectin , insulin , HOMAIR , Matsuda ISI , M-value ; all P.0·05 ) . In conclusion , nutritional stress imposed by dietary restriction and refeeding reveals a GI/fibre effect in healthy non-obese subjects . LGI foods rich in fibre may improve glucose metabolism during the vulnerable refeeding phase of a weight cycle BACKGROUND Insulin sensitivity ( Si ) is improved by weight loss and exercise , but the effects of the replacement of saturated fatty acids ( SFAs ) with monounsaturated fatty acids ( MUFAs ) or carbohydrates of high glycemic index ( HGI ) or low glycemic index ( LGI ) are uncertain . OBJECTIVE We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome . DESIGN We conducted a 5-center , parallel design , r and omized controlled trial [ RISCK ( Reading , Imperial , Surrey , Cambridge , and Kings ) ] . The primary and secondary outcomes were changes in Si ( measured by using an intravenous glucose tolerance test ) and cardiovascular risk factors . Measurements were made after 4 wk of a high-SFA and HGI ( HS/HGI ) diet and after a 24-wk intervention with HS/HGI ( reference ) , high-MUFA and HGI ( HM/HGI ) , HM and LGI ( HM/LGI ) , low-fat and HGI ( LF/HGI ) , and LF and LGI ( LF/LGI ) diets . RESULTS We analyzed data for 548 of 720 participants who were r and omly assigned to treatment .  The median Si was 2.7 × 10(-4 ) mL · μU(-1 ) · min(-1 ) ( interquartile range : 2.0 , 4.2 × 10(-4 ) mL · μU(-1 ) · min(-1 ) ) , and unadjusted mean percentage changes ( 95 % CIs ) after 24 wk treatment ( P = 0.13 ) were as follows : for the HS/HGI group , -4 % ( -12.7 % , 5.3 % ) ; for the HM/HGI group , 2.1 % ( -5.8 % , 10.7 % ) ; for the HM/LGI group , -3.5 % ( -10.6 % , 4.3 % ) ; for the LF/HGI group , -8.6 % ( -15.4 % , -1.1 % ) ; and for the LF/LGI group , 9.9 % ( 2.4 % , 18.0 % ) . Total cholesterol ( TC ) , LDL cholesterol , and apolipoprotein B concentrations decreased with SFA reduction . Decreases in TC and LDL-cholesterol concentrations were greater with LGI . Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations . CONCLUSIONS This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si . Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects , with tentative evidence of improvements in Si in the LF-treatment group . This trial was registered at clinical trials.gov as IS RCT N29111298 OBJECTIVE To examine the relation between weight change and weight fluctuation ( cycling ) and mortality in middle-aged men . METHODS A prospect i ve study of 5608 men aged 40 to 59 years at screening , drawn from one general practice in each of 24 British towns . Changes in weight observed during a 12- to 14-year period were related to mortality during the subsequent 8 years . RESULTS There were 943 deaths from all causes : 458 cardiovascular disease ( CVD ) and 485 non-CVD deaths . Those with stable weight or weight gain had the lowest total , CVD , and non-CVD mortality . Sustained weight loss or weight fluctuation ( loss-gain or gain-loss )  showed a significantly higher mortality risk than stable weight even after adjustment for lifestyle variables ( relative risk [ 95 % confidence interval ] , 1.60 [ 1.32 - 1.95 ] , 1.50 [ 1.17 - 1.91 ] , and 1.63 [ 1.24 - 2.14 ] , respectively ) . Adjustment or exclusion of men with preexisting disease markedly attenuated the increased risk of CVD and total mortality associated with sustained weight loss and weight gain-weight loss . In long-term nonsmokers , any weight loss since screening was associated with an increased risk of mortality , but this was markedly attenuated by adjustment for preexisting disease . Recent ex-smokers showed the most marked increase in mortality associated with sustained weight loss . CONCLUSIONS The increased mortality in middle-aged men with sustained weight loss and weight fluctuation ( cycling ) is determined to a major extent by disadvantageous lifestyle factors and preexisting disease . The evidence suggests that weight loss and weight fluctuation ( cycling ) in these men does not directly increase the risk of death OBJECTIVE Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM , whereas dietary fiber is suspected to reduce incidence . These hypotheses have not been evaluated prospect ively . RESEARCH DESIGN AND METHODS We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease , who were 40–75 years of age in 1986 .  Diet was assessed at baseline by a vali date d semiquantitative food frequency question naire . During 6-years of follow-up , 523 incident cases of NIDDM were documented . RESULTS The dietary glycemic index ( an indicator of carbohydrate 's ability to raise blood glucose levels ) was positively associated with risk of NIDDM after adjustment for age , BMI , smoking , physical activity , family history of diabetes , alcohol consumption , cereal fiber , and total energy intake . Comparing the highest and lowest quintiles , the relative risk ( RR ) of NIDDM was 1.37 ( 95 % CI , 1.02–1.83 , P trend = 0.03 ) .  Cereal fiber  was inversely associated with risk of NIDDM ( RR = 0.70 ; 95 % CI , 0.51–0.96 , P trend = 0.007 ; for > 8.1 g/day vs. < 3.2 g/day ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM ( RR = 2.17 , 95 % CI , 1.04–4.54 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM  in men . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM The risk of coronary heart disease ( CHD ) is influenced by family history , insulin sensitivity ( IS ) , and diet . Adiposity affects CHD and IS . The cellular mechanism of IS is thought to involve the adipocyte cytokine tumor necrosis factor-alpha ( TNF-alpha ) . Insulin-stimulated glucose uptake in isolated subcutaneous and omental adipocytes obtained during elective surgery was measured in 61 premenopausal women , 24 with a parental history ( PH ) of CHD .  In vivo IS was measured using the  short insulin tolerance test ( SITT )  in 28 women , 16 with PH-CHD , before and 3 weeks after r and omization to a  low glycemic index ( LGI ) or high glycemic index ( HGI ) diet .  In vitro adipocyte IS and TNF-alpha production was measured following dietary modification . On the habitual diet , in vitro insulin-stimulated glucose uptake in adipocytes as a percentage increase over basal was less in women with PH-CHD than in those without it ( presented as the median with 95 % confidence limits : subcutaneous , 28 % ( 17 % to 39 % ) v 96 % ( 70 % to 120 % ) , P < .01 ) ; omental , 40 % ( 28 % to 52 % ) v 113 % ( 83 % to 143 % ) , P < .01 ) . In vivo IS in 16 PH-CHD subjects and 12 controls before dietary r and omization was similar , and increased in both groups consuming a LGI versus HGI diet ( PH-CHD , 0.31 ( 0.26 to 0.37 ) v 0.14 ( 0.10 to 0.24 ) mmol/L/min , P < .01 ; controls , 0.31 ( 0.1 to 0.53 ) v 0.15 ( 0.06 to 0.23 ) mmol/L/min , P < .05 ) . Adipocyte IS was greater in PH-CHD women on a LGI versus HGI diet ( subcutaneous , 50 % ( 20 % to 98 % ) v 13 % ( 1 % to 29 % ) ; omental , 
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There is also a Cochrane systematic review which suggests that the GI may play a role in promoting weight loss .
Therefore , the literature , as it currently st and s , presents a convincing case for the clinical application of the GI in the management of body weight and glucose homeostasis .
In this issue of the British Journal of Nutrition , Lagerpusch et al. observed that in the dynamic phase of weight gain , a high-fibre , low-GI diet  reduced daytime measurements of interstitial glucose when compared with an energy-matched lowfibre , high-GI diet .
Furthermore , the deterioration in insulin sensitivity induced by refeeding was attenuated , though the effects of the two dietary interventions were resolved at the end of the refeeding phase .
The authors do not offer any suggestions as to which specific dietary manipulation they believe may be driving their observed improvements in glucose metabolism and insulin sensitivity .
In two large-scale epidemiological studies ( the Nurses ’ Health Study and Health Professionals Follow-up Study ) , it has been demonstrated that the risk of developing type 2 diabetes increases with a concomitant increase in dietary glycaemic load ( the GI multiplied by the amount of carbohydrate consumed ) and a reduction in fibre consumption .
The uncoupling of these two aspects of the diet meant that the relationship disappeared or was significantly weaker .
Furthermore , the Reading , Imperial , Surrey , Cambridge , and Kings ( RISCK ) study , a large multicentre dietary intervention in over 500 adults at risk of CVD , aim ed to eluci date how dietary changes may influence insulin sensitivity and other CVD risk factors .
A surprising finding of the study was the absence of an improvement in insulin sensitivity following a lowv .
high-GI diet .
This raises the intriguing question of whether the dietary deconstruction seen in most nutritional interventions , in line with the current reductionist scientific approach , is actually detrimental .
By controlling for every aspect of the diet , could we actually be missing important physiological effects that occur from dietary manipulations which often go h and -in-h and , like GI and dietary fibre ?
In the gastrointestinal tract , low-GI diets with a high fibre content slow gastric emptying , reduce digesta transit rate and alter the luminal environment , all of which will ultimately delay glucose absorption and result in an ameliorated insulin response .
For example , high-fibre , low-GI diets may promote insulin sensitivity by improving metabolic flexibility , i.e. the ability of an organism to modify fuel oxidation in response to changes in nutrient availability .
Metabolic flexibility enables an efficient transition from lipid oxidation and high rates of fatty acid uptake during the fasted state , to suppression of lipid oxidation and increased glucose uptake and utilisation in response to insulin stimulation .