***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: Patients with insulin resistance often manifest increased intramyocellular lipid ( IMCL ) along with increased visceral adipose tissue . This study was design ed to determine whether the insulin sensitizer drugs pioglitazone and metformin would improve glucose intolerance and insulin sensitivity by decreasing IMCL . In this study , 23 generally healthy subjects with impaired glucose tolerance were r and omized to receive either pioglitazone 45 mg/day or metformin 2,000 mg/day for 10 wk . Before and after treatment , we measured insulin sensitivity and abdominal subcutaneous and visceral adipose tissue with CT scanning . In addition , muscle biopsies were performed for measurement of IMCL and muscle oxidative enzymes . After treatment with pioglitazone , 2-h glucose fell from 9.6 mmol/l ( 172 mg/dl ) to 6.1 mmol/l ( 119 mg/dl ) , whereas there was no change in 2-h glucose with metformin . With pioglitazone treatment , there was a 65 % increase in insulin sensitivity along with a 34 % decrease in IMCL ( both P < or = 0.002 ) . This decrease in IMCL was not due to increased muscle lipid oxidation , as there were no changes in muscle lipid oxidative enzymes . However , pioglitazone result ed in a 2.6-kg weight gain along with a significant decrease in the visceral-to-subcutaneous adipose tissue ratio . In contrast , metformin treatment result ed in no change in insulin sensitivity , IMCL , oxidative enzymes , or adipose tissue volumes .  Pioglitazone improved glucose tolerance and insulin sensitivity by reducing IMCL . This reduction in IMCL was not due to an increase in muscle lipid oxidation but to a diversion of lipid from ectopic sites into subcutaneous adipose tissue OBJECTIVE The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance ( IGT ) . Participants with IGT are at high risk for cardiovascular disease ( CVD ) , with a marked increase in the number and severity of CVD risk factors . We prospect ively assessed the impact of our interventions on hypertension , dyslipidemia , and CVD events . RESEARCH DESIGN AND METHODS The study group consisted of 3,234 individuals with IGT r and omly assigned to receive intensive lifestyle intervention , metformin , or placebo . Annual assessment of blood pressure , lipids , electrocardiogram , and CVD events was undertaken . RESULTS Hypertension was present in 30 % of participants at study entry and then increased in the placebo and metformin groups , although it significantly decreased with intensive lifestyle intervention . Triglyceride levels fell in all treatment groups , but fell significantly more with intensive lifestyle intervention . Total cholesterol and LDL cholesterol levels were similar among treatment groups . Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up , the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27 - 28 % less for hypertension and 25 % less for hyperlipidemia compared with placebo and metformin groups . Over an average of 3 years , 89 CVD events from 64 participants were positively adjudicated study wide , with no differences among treatment groups . CONCLUSIONS Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy . Although no differences in CVD events were noted after 3 years , achieved risk factor modifications suggest that longer intervention may reduce CVD event rates AIMS This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations . METHODS Nineteen obese patients with impaired glucose tolerance ( IGT ) were treated with either metformin or placebo in a r and omized , double-blind , placebo-controlled , cross-over study . Insulin secretion and insulin resistance were quantified using the homeostasis model assessment ( HOMA ) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose ( SSPG ) . RESULTS The average benefit of metformin was 0.6 mmol/l for glucose ( 95 % confidence interval ( CI ) 0.2 - 0.9 P = 0.002 ) , 2.8 pmol/l for insulin ( 95 % CI 0.2 - 5.4 , P = 0.019 ) . Insulin resistance , as quantified by HOMA , was improved by 1.1 ( 95 % CI 0.2 - 2.0 , P = 0.004 ) , without any change in insulin secretion . Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period , as was the SSPG concentration . However , both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo . CONCLUSIONS These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure . In contrast , neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia Several studies have demonstrated that type 2 diabetes mellitus ( DM ) can be prevented/delayed in subjects with impaired glucose tolerance ( IGT ) by using pharmacologic agents and /or lifestyle interventions . However , a number of challenges remain , including the translation of lifestyle programmes to the general population and the need to achieve greater risk reductions by using pharmacologic approaches . IGT , like DM , is characterized by insulin resistance , β‐cell dysfunction and increased hepatic glucose production . We believe that the use of combination diabetes therapy would be a particularly effective diabetes prevention strategy . In this context , we initiated the Canadian Normoglycemia Outcomes Evaluation ( CANOE ) study , a moderately sized , r and omized , double‐blind , controlled trial . The primary objective of CANOE is to determine whether treatment with metformin plus rosiglitazone , in addition to a healthy living lifestyle programme , will prevent the development of DM . The secondary objective of CANOE is to determine whether this treatment approach will improve cardiovascular risk factors associated with IGT . A total of 200 patients will be recruited in Toronto and London , Ontario , and followed for an average of 4 years ( range 3–5 years ) . Active treatment with metformin ( 500 mg ) plus rosiglitazone ( 2 mg ) , administered as one capsule twice daily , will be compared to matched placebo .  Subjects will be eligible for r and omization if they have IGT and are between the ages of 30–75 years . The primary outcome will be the development of new‐onset DM , diagnosed by either two fasting plasma glucose values of ≥7 mmol/l or one positive oral glucose tolerance test with a 2‐h plasma glucose value of > 11.0 mmol/l during the active drug phase of the trial . With a sample size of 100 participants per group , we will be able to detect a relative risk reduction of 45 % , with a two‐sided log‐rank test with a significance level of 0.05 and 80 % power , assuming that the median time to progression is 8 years in the control group and that participants will be recruited over 2 years and followed for an average of 4 years . In conclusion , the CANOE study will determine whether combination pharmacological therapy combined with a lifestyle intervention programme can significantly modify the development of diabetes in high‐risk Canadians The research ers conducted this study to test the hypothesis that risk of  type 2 diabetes  is less following reductions in body size and central adiposity . The Diabetes Prevention Program ( DPP ) recruited and r and omized individuals with impaired glucose tolerance to treatment with placebo , metformin , or lifestyle modification .  Height , weight , waist circumference , and subcutaneous and visceral fat at L2-L3 and L4-L5 by computed tomography were measured at baseline and at 1 year . Cox proportional hazards models assessed by sex the effect of change in these variables over the 1st year of intervention upon development of diabetes over subsequent follow-up in a subset of 758 participants . Lifestyle reduced visceral fat at L2-L3 ( men −24.3 % , women −18.2 % ) and at L4-L5 ( men −22.4 % , women −17.8 % ) , subcutaneous fat at L2-L3 ( men −15.7 % , women −11.4 % ) and at L4-L5 ( men −16.7 % , women −11.9 % ) , weight ( men −8.2 % , women −7.8 % ) , BMI ( men −8.2 % , women −7.8 % ) , and waist circumference ( men −7.5 % , women −6.1 % ) . Metformin  reduced weight ( −2.9 % ) and BMI ( −2.9 % ) in men and subcutaneous fat ( −3.6 % at L2-L3 and −4.7 % at L4-L5 ) , weight ( −3.3 % ) , BMI ( −3.3 % ) , and waist circumference ( −2.8 % ) in women . Decreased diabetes risk by lifestyle intervention was associated with reductions of body weight , BMI , and central body fat distribution after adjustment for age and self-reported ethnicity . Reduced diabetes risk with lifestyle intervention may have been through effects upon both overall body fat and central body fat but with metformin appeared to be independent of body fat The effect of metformin ( 1000 mg twice a day ) on markers of endothelial activation , inflammation , and coagulation was investigated in subjects with impaired glucose tolerance ( IGT ) in a 16-wk , r and omized , placebo-controlled , double-blind study . Soluble intercellular adhesion molecule , soluble vascular cell adhesion molecule , C-reactive protein , TNFalpha , von Willebr and factor , and tissue plasminogen activator were measured at baseline and at the end of the trial . Subjects with IGT ( n = 55 , 14 males and 41 females ) , aged 48.4 + /- 9.6 yr with a body mass index of 31.4 + /- 5.6 kg/m(2 ) , were studied . All participants followed a 1-month stabilization period in their diet and physical activity . Afterward , 29 subjects were assigned to the treatment group and 26 to the control group . A significant reduction in weight , fasting plasma glucose , soluble intercellular adhesion molecule ( 306 + /- 75 vs. 268 + /- 61 ng/ml , P = 0.029 ) , soluble vascular cell adhesion molecule ( 595 + /- 114 vs. 508 + /- 126 ng/ml , P = 0.006 ) , and von Willebr and factor ( 124 + /- 34 vs. 94 + /- 34 % , P = 0.001 ) was seen in the treatment group , whereas tissue plasminogen activator , TNFalpha , and C-reactive protein levels did not change . No change was seen in the control group . Thus , metformin improves the plasma levels of some markers of endothelial activation and coagulation in subjects with IGT , whereas it has no effect on markers of inflammation AIMS To evaluate the effect of metformin on glucose metabolism , insulin sensitivity and rate of conversion diabetes in people with impaired glucose tolerance ( IGT ) . METHODS Seventy subjects with IGT were r and omized under double-blind conditions to receive either placebo ( n = 37 ) or metformin ( n = 33 ) at a dosage of 250 mg three times daily for a duration of 12 months . Glycaemic control , plasma insulin and other biochemical indexes were assessed before and after 3 , 6 and 12 months . RESULT At 12 months the conversion rate to diabetes was 16.2 % in the placebo group compared to 3.0 % for the metformin group ( P = 0.011 ) . Of subjects treated with metformin for 12 months , 84.9 % became normoglycaemic compared to 51.4 % of those receiving the placebo . Significant improvements in fasting glucose , glucose tolerance and insulin sensitivity were found at 12 months and at intermediate clinic assessment s. CONCLUSIONS Metformin can improve glucose metabolism in IGT patients and may be a treatment option in their management of IGT subjects Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM 
    Output:
    
Metformin decreases the rate of conversion from prediabetes to diabetes .