***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 
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    ***EXAMPLES*** 
    Input: Objective To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes  among initially healthy participants . Design Prospect i ve cohort study with estimates of relative risk adjusted for sex , age , years of university education , total energy intake , body mass index , physical activity , sedentary habits , smoking , family history of diabetes , and personal history of hypertension . Setting Spanish university department . Participants 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years . Main outcome measures Dietary habits assessed at baseline with a vali date d 136 item food frequency question naire and scored on a nine point index . New cases of diabetes confirmed through medical reports and an additional detailed question naire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up . Confirmed cases of type 2 diabetes . Results Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes . The incidence rate ratios adjusted for sex and age were 0.41 ( 95 % confidence interval 0.19 to 0.87 ) for those with moderate adherence ( score 3 - 6 ) and 0.17 ( 0.04 to 0.75 ) for those with the highest adherence ( score 7 - 9 ) compared with those with low adherence ( score < 3 ) . In the fully adjusted analyses the results were similar . A two point increase in the score was associated with a 35 % relative reduction in the risk of diabetes ( incidence rate ratio 0.65 , 0.44 to 0.95 ) , with a significant inverse linear trend ( P=0.04 ) in the multivariate analysis . Conclusion Adherence to a Mediterranean diet is associated with a reduced risk of diabetes Although acute alkaloid caffeine ( CAF ) ingestion results in an impaired glucose tolerance , chronic coffee ( RCOF ) ingestion decreases the risk of developing type 2 diabetes . This study examines the hypothesis that CAF ingestion impairs glucose tolerance to a greater extent than RCOF and that the ingestion of decaffeinated coffee ( DECAF ) results in a positive effect . Eleven healthy males underwent 4 double-blinded r and omized trials . Each trial included the ingestion of either : 1 ) CAF in capsule form ( 4.45 mg/kg body weight ) , 2 ) RCOF ( 4.45 mg/kg body weight caffeine ) , 3 ) dextrose ( placebo , PL ) in capsule form , or 4 ) DECAF ( equal in volume to the RCOF trial ) , followed 1-h later by a 2-h oral glucose tolerance test . Blood sample s were collected at baseline ( -30 ) , 0 ( time of treatment ingestion ) , 60 ( initiation of oral glucose tolerance test ) , 75 , 90 , 120 , 150 , and 180 min . Area under the curve for glucose and insulin were higher ( P < or = 0.05 ) following CAF than both PL and DECAF and , although a similar trend ( P = 0.07 ) was observed following RCOF compared with DECAF , the effect was less pronounced . Interestingly , DECAF result ed in a 50 % lower glucose response ( P < or = 0.05 ) than PL , suggesting that the effects of PL and DECAF on glucose tolerance are not the same . These findings suggest that the effects of CAF and RCOF are not identical and may provide a partial explanation as to why acute CAF ingestion impairs glucose tolerance while chronic RCOF ingestion protects against type 2 diabetes BACKGROUND Caffeine ingestion decreases the insulin sensitivity index ( ISI ) for an oral-glucose-tolerance test ( OGTT ) and decreases insulin-induced glucose disposal in lean male subjects during a hyperinsulinemic clamp . OBJECTIVE We examined the effects of caffeine ingestion on insulin and glucose homeostasis in obese men before and after a nutrition and exercise intervention .  DESIGN Nine sedentary , obese [ body mass index ( in kg/m(2 ) ) : 34.0 + /- 1.0 ] men who had refrained from exercise and caffeine ingestion for 48 h underwent 2 oral-glucose-tolerance tests ( OGTTs ) . The subjects r and omly received caffeine ( 5 mg/kg ) or placebo 1 h before each OGTT . After a 12-wk nutrition and exercise intervention , during which time the subjects avoided dietary caffeine , the OGTTs were repeated . RESULTS The intervention result ed in decreases ( P < or = 0.05 ) in body weight ( 8.5 + /- 1.5 kg ) , percentage body fat ( 2.8 + /- 0.7 % ) , and fasting glucose , insulin , and proinsulin concentrations and increases in the ISI for the placebo OGTT ( P < or = 0.05 ) . Caffeine caused a greater ( P < or = 0.05 ) OGTT insulin response and a lower ( P < or = 0.05 ) ISI both before and after weight loss . The proinsulin-insulin ratio indicated that neither weight loss nor caffeine affected the nature of the beta cell secretion of insulin . CONCLUSIONS A nutrition and exercise intervention improved , whereas caffeine ingestion impaired , insulin-glucose homeostasis in obese men . The results are consistent with previous findings that caffeine ingestion contributes to insulin resistance BACKGROUND The ingestion of caffeine ( 5 mg/kg body weight ) and a 75-g oral glucose load has been shown to elicit an acute insulin-insensitive environment in healthy and obese individuals and in those with type 2 diabetes . OBJECTIVE In this study we investigated whether a similar impairment in blood glucose management exists when coffee and foods typical of a Western diet were used in a similar protocol . DESIGN Ten healthy men underwent 4 trials in a r and omized order . They ingested caffeinated ( 5 mg/kg ) coffee ( CC ) or the same volume of decaffeinated coffee ( DC ) followed 1 h later by either a high or low glycemic index ( GI ) cereal ( providing 75 g of carbohydrate ) mixed meal tolerance test . RESULTS CC with the high GI meal result ed in 147 % , 29 % , and 40 % greater areas under the curve for glucose ( P < 0.001 ) , insulin ( NS ) , and C-peptide ( P < 0.001 ) , respectively , compared with the values for DC . Similarly , with the low GI treatment , CC elicited 216 % , 44 % , and 36 % greater areas under the curve for glucose ( P < 0.001 ) , insulin ( P < 0.01 ) , and C-peptide ( P < 0.01 ) , respectively . Insulin sensitivity was significantly reduced ( 40 % ) with the high GI treatment after CC was ingested compared with DC ; with the low GI treatment , CC ingestion result ed in a 29 % decrease in insulin sensitivity , although this difference was not significant . CONCLUSION The ingestion of CC with either a high or low GI meal significantly impairs acute blood glucose management and insulin sensitivity compared with ingestion of DC . Future investigations are warranted to determine whether CC is a risk factor for insulin resistance BACKGROUND Accumulating evidence suggests that certain dietary polyphenols have biological effects in the small intestine that alter the pattern of glucose uptake . Their effects , however , on glucose tolerance in humans are unknown . OBJECTIVE The objective was to investigate whether chlorogenic acids in coffee modulate glucose uptake and gastrointestinal hormone and insulin secretion in humans . DESIGN In a 3-way , r and omized , crossover study , 9 healthy fasted volunteers consumed 25 g glucose in either 400 mL water ( control ) or 400 mL caffeinated or decaffeinated coffee ( equivalent to 2.5 mmol chlorogenic acid/L ) . Blood sample s were taken frequently over the following 3 h. RESULTS Glucose and insulin concentrations tended to be higher in the first 30 min after caffeinated coffee consumption than after consumption of decaffeinated coffee or the control ( P < 0.05 for total and incremental area under the curve for glucose and insulin ) . Glucose-dependent insulinotropic polypeptide secretion decreased throughout the experimental period ( P < 0.005 ) , and glucagon-like peptide 1 secretion increased 0 - 120 min postpr and ially ( P < 0.01 ) after decaffeinated coffee consumption compared with the control . Glucose and insulin profiles were consistent with the known metabolic effects of caffeine . However , the gastrointestinal hormone profiles were consistent with delayed intestinal glucose absorption . CONCLUSIONS Differences in plasma glucose , insulin , and gastrointestinal hormone profiles further confirm the potent biological action of caffeine and suggest that chlorogenic acid might have an antagonistic effect on glucose transport . Therefore , a novel function of some dietary phenols in humans may be to attenuate intestinal glucose absorption rates and shift the site of glucose absorption to more distal parts of the intestine We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake , glycogen synthase ( GS ) activity , and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic ( 100 microU/ml ) clamp . On two occasions , seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp . Caffeine ( 5 mg/kg ) or placebo was administered in a r and omized , double-blind fashion 1 h before the clamp . During the clamp , whole-body glucose disposal was reduced ( P < 0.05 ) in caffeine ( 37.5 + /- 3.1 micromol x min(-1 ) x kg(-1 ) ) vs. placebo ( 54.1 + /- 2.9 micromol x min(-1 ) x kg(-1 ) ) . In accordance , the total area under the curve over 100 min ( AUC(0 - -100 min ) ) for insulin-stimulated glucose uptake in caffeine was reduced ( P < 0.05 ) by approximately 50 % in rested and exercised muscle . Caffeine also reduced ( P < 0.05 ) GS activity before and during insulin infusion in both legs . Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo . Insulin increased insulin receptor tyrosine kinase ( IRTK ) , insulin receptor substrate 1-associated phosphatidylinositol ( PI ) 3-kinase activities , and Ser(473 ) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs . Furthermore , insulin significantly decreased glycogen synthase kinase-3alpha ( GSK-3alpha ) activity equally in both legs . Caffeine did not alter insulin signaling in either leg . Plasma epinephrine and muscle cAMP concentrations were increased in caffeine . We conclude that 1 ) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle ; 2 ) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK , PI 3-kinase , PKB/Akt , or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations ; and 3 ) exercise reduces the detrimental effects of caffeine on insulin action in muscle Context Caffeine intake from coffee has been associated with a lower incidence of diabetes . Research ers have not studied the relationship of green tea , a popular beverage in Japan , where the incidence of diabetes is increasing rapidly . Contributions The authors estimated the intake of caffeine-containing beverages in a community-based survey in Japan and measured the 5-year incidence of diabetes . Greater intake of green tea or coffee was associated with a reduced incidence of diabetes . The effect of green tea was largely observed in women , was dose-related , and reflected caffeine intake . Implication s Higher intake of caffeine , whether from coffee or green tea , is associated with a lower incidence of diabetes . The Editors The prevalence of type 2 diabetes has increased worldwide , particularly in Asian countries where it was previously low ( 1 ) . In Japan , population -based studies have shown a 2-fold increase in the prevalence of diabetes during the past 2 decades , from 5 % to 10 % to 10 % to 15 % ( 2 ) . Several cohort studies done in Europe and in the United States reported an association between coffee consumption , a major source of caffeine , and reduced risk for diabetes ( 3 - 7 ) . Although these studies did not show any association between consumption of black tea and the risk for diabetes , they did not examine the effect of green or oolong teas , major sources of caffeine in Asian countries . Consumption of green tea is common in Japan ; 80 % of the population drinks green 
    Output:
    
Conclusion Acute caffeine ingestion reduces insulin sensitivity in healthy subjects .
Thus , in the short term , caffeine might shift glycemic homeostasis toward hyperglycemia .