human
***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: AIMS We examined the effects of physical activity with or without dietary restriction for 3 months on regional fat and insulin sensitivity and compared the effect of total energy expenditure from all levels of physical activity with that of physical activity energy expenditure from moderate-to-vigorous exercise in obese women with Type 2 diabetes . METHODS In this r and omized , controlled trial , we assessed change of body weight , abdominal visceral fat area , subcutaneous fat area and insulin sensitivity , expressed as K(ITT ) , and monitored total energy expenditure and physical activity energy expenditure using an accelerometer during a 12-week intervention in four groups : control , diet , exercise and diet plus exercise . RESULTS The mean body mass index was 28.0 + /- 2.7 kg/m(2 ) and the mean duration of diabetes was 8 + /- 6 years . Both the diet and diet plus exercise groups showed significant body weight loss compared with the control group ( P < 0.05 ) . However , the visceral fat area was reduced only in the diet and exercise group ( P = 0.017 ) and the subcutaneous fat area was reduced only in the diet group ( P = 0.009 ) . Mean energy intake was an independent determinant of the change in subcutaneous fat area ( P = 0.020 ) and mean total anergy expenditure was an independent determinant of visceral fat area ( P = 0.002 ) . Insulin sensitivity K(ITT ) was associated with physical activity energy expenditure ( P = 0.006 ) , energy intake ( P = 0.047 ) and the change in fructosamine level ( P = 0.016 ) but not with changes in body weight , subcutaneous fat area , visceral fat area or adipokine level . CONCLUSIONS Exercise had an additive effect to dietary restriction on visceral fat reduction . Visceral fat area was associated with total energy expenditure , but insulin sensitivity was associated with physical activity energy expenditure BACKGROUND & AIMS We determined the effects of acute and chronic calorie restriction with either a low-fat , high-carbohydrate ( HC ) diet or a low-carbohydrate ( LC ) diet on hepatic and skeletal muscle insulin sensitivity . METHODS Twenty-two obese subjects ( body mass index , 36.5 + /- 0.8 kg/m2 ) were r and omized to an HC ( > 180 g/day ) or LC ( < 50 g/day ) energy-deficit diet . A euglycemic-hyperinsulinemic clamp , muscle biopsy specimens , and magnetic resonance spectroscopy were used to determine insulin action , cellular insulin signaling , and intrahepatic triglyceride ( IHTG ) content before , after 48 hours , and after approximately 11 weeks ( 7 % weight loss ) of diet therapy . RESULTS At 48 hours , IHTG content decreased more in the LC than the HC diet group ( 29.6 % + /- 4.8 % vs 8.9 % + /- 1.4 % ; P < .05 ) but was similar in both groups after 7 % weight loss ( LC diet , 38.0 % + /- 4.5 % ; HC diet , 44.5 % + /- 13.5 % ) . Basal glucose production rate decreased more in the LC than the HC diet group at 48 hours ( 23.4 % + /- 2.2 % vs 7.2 % + /- 1.4 % ; P < .05 ) and after 7 % weight loss ( 20.0 % + /- 2.4 % vs 7.9 % + /- 1.2 % ; P < .05 ) . Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7 % weight loss ( 48.4 % + /- 14.3 % ; P < .05 ) . In both groups , insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29 % + /- 13 % and phosphorylation of Akt and insulin receptor substrate 1 increased by 35 % + /- 9 % and 36 % + /- 9 % , respectively , after 7 % weight loss ( all P < .05 ) . CONCLUSIONS Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism ; 48 hours of calorie restriction affects the liver ( IHTG content , hepatic insulin sensitivity , and glucose production ) , whereas moderate weight loss affects muscle ( insulin-mediated glucose uptake and insulin signaling ) BACKGROUND & AIMS Despite increasing use of various imaging examinations for non-invasive assessment of hepatic steatosis ( HS ) , their relative accuracy is unknown . The objective of this study is to prospect ively compare the accuracy of computed tomography ( CT ) , dual gradient echo magnetic resonance imaging ( DGE-MRI ) , proton magnetic resonance spectroscopy ( (1)H-MRS ) , and ultrasonography ( US ) for the diagnosis and quantitative estimation of HS . METHODS A total of 161 consecutive potential living liver donors underwent US ( performed by two independent radiologists , US1 and US2 ) , CT , DGE-MRI , (1)H-MRS , and liver biopsy on the same day . Using the histologic degree of HS as the reference st and ard , we compared the diagnostic performance of US1 , US2 , CT , DGE-MRI , and (1)H-MRS for diagnosing HS > or= 5 % and HS > or= 30 % and compared the accuracy of CT , DGE-MRI , and (1)H-MRS in the quantitative estimation of HS . RESULTS  DGE-MRI and (1)H-MRS  significantly outperformed CT and US for the diagnosis of HS5 % .  DGE-MRI  showed a tendency of higher accuracy than the other examinations for diagnosing HS > or= 30 % . The cross-vali date d sensitivity and specificity of DGE-MRI  at the optimal cut-off were 76.7 % and 87.1 % , respectively , for diagnosing HS > or= 5 % and 90.9 % and 94 % , respectively , for diagnosing HS > or= 30 % . The cross-vali date d Bl and -Altman 95 % limits of agreement between the estimated degree of HS on imaging examinations and the histologic degree of HS , were the narrowest with DGE-MRI , yielding -12.7 % to 12.7 % . CONCLUSIONS Among CT , DGE-MRI , (1)H-MRS , and US , DGE-MRI is the most accurate method for the diagnosis and quantitative estimation of HS . Therefore , DGE-MRI may be the preferred imaging examination for the non-invasive assessment of HS Despite the increasing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , the criteria used to diagnose the disorder remain poorly defined . Localized proton magnetic resonance spectroscopy ( MRS ) accurately measures hepatic triglyceride content ( HTGC ) but has been used only in small research studies . Here , MRS was used to analyze the distribution of HTGC in 2,349 participants from the Dallas Heart Study ( DHS ) . The reproducibility of the procedure was vali date d by showing that duplicate HTGC measurements were high correlated ( r = 0.99 , P < 0.001 ) and that the coefficient of variation between measurements was low ( 8.5 % ) . Intake of a high-fat meal did not significantly affect the measurements , and values were similar when measurements were made from the right and left hepatic lobes . To determine the " upper limit of normal " for HTGC , the distribution of HTGC was examined in the 345 subjects from the DHS who had no identifiable risk factors for hepatic steatosis ( nonobese , nondiabetic subjects with minimal alcohol consumption , normal liver function tests , and no known liver disease ) . The 95th percentile of HTGC in these subjects was 5.56 % , which corresponds to a hepatic triglyceride level of 55.6 mg/g . With this value as a cutoff , the prevalence of hepatic steatosis in Dallas County was estimated to be 33.6 % . Thus MRS provides a sensitive , quantitative , noninvasive method to measure HTGC and , when applied to a large urban US population , revealed a strikingly high prevalence of hepatic steatosis OBJECTIVE Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes , and conjunctive use of weight loss medication has been advocated . The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment , using behavioral intervention ( Int ) combined with r and omized , double-blinded , placebo (P)-controlled treatment with orlistat ( O ) . RESEARCH DESIGN AND METHODS Metabolic control , insulin sensitivity ( IS ) , regional fat distribution , and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding r and omization .  Weight loss was equivalent in the Int+O and Int+P groups , respectively ( -10.3 + /- 1.3 vs. -8.9 + /- 1.1 % ) , and there were identical decreases in visceral adipose tissue ( VAT ) , fat mass ( FM ) , thigh adiposity , and hepatic steatosis . RESULTS Weight loss result ed in substantial improvement ( P < 0.001 ) in HbA(1c ) ( -1.6 + /- 0.3 vs. -1.0 + /- 0.4 % ; NS between groups ) . IS improved significantly more with orlistat ( Delta2.2 + /- 0.4 vs. Delta1.2 + /- 0.4 mg . min(-1 ) . kg(-1 ) fat-free mass [ FFM ] ; P < 0.05 ) , and plasma free fatty acid ( FFA ) levels were strongly correlated with IS ( r = 0.56 ; P < 0.001 ) . Orlistat caused greater reductions in fasting plasma FFA ( Delta-154 + /- 22 vs. Delta-51 + /- 33 micro mol/l ; P < 0.05 ) , insulin-suppressed FFA ( Delta-119 + /- 23 vs. Delta-87 + /- 34 micro mol/l ; P < 0.05 ) , and fasting plasma glucose ( FPG ; -62 + /- 9 vs. -32 + /- 8 mg/dl ; P = 0.02 ) . Changes in HbA(1c ) were correlated with DeltaIS ( r = -0.41 ; P < 0.01 ) but not with weight loss per se . CONCLUSIONS At equivalent weight loss , conjunctive use of orlistat result ed in greater improvement in FFA levels and IS OBJECTIVE Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease ( NAFLD ) . However , its efficacy in patients with type 2 diabetes is unproven . RESEARCH DESIGN AND METHODS Look AHEAD ( Action for Health in Diabetes ) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes , who were r and omly assigned to an intensive lifestyle intervention ( ILI )  to induce a minimum weight loss of 7 % or a control group who received diabetes support and education ( DSE ) . In the Fatty Liver Ancillary Study , 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months . We defined steatosis > 5.5 % as NAFLD . RESULTS Participants were 49 % women and 68 % white . The mean age was 61 years , mean BMI was 35 kg/m2 , mean steatosis was 8.0 % , and mean aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) were 20.5 and 24.2 units/l , respectively . After 12 months , participants assigned to ILI ( n = 46 ) lost more weight ( −8.5 vs. −0.05 % ; P < 0.01 ) than those assigned to DSE and had a greater decline in steatosis ( −50.8 vs. −22.8 % ; P = 0.04 ) and in A1C ( −0.7 vs. −0.2 % ; P = 0.04 ) . There were no significant 12-month changes in AST or ALT levels . At 12 months , 26 % of DSE participants and 3 % ( 1 of 31 ) of ILI participants without NAFLD at baseline developed NAFLD ( P < 0.05 ) . CONCLUSIONS A 12-month intensive lifestyle intervention in patients with type 2 diabetes  reduces steatosis and incident NAFLD To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes , we used (1)H magnetic resonance spectroscopy to assess intrahepatic lipid ( IHL ) and intramyocellular lipid ( IMCL ) content in conjunction with hyperinsulinemic-euglycemic clamps using [6,6-(2)H(2)]glucose to assess 
    Output:
    
agent
***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: AIMS We examined the effects of physical activity with or without dietary restriction for 3 months on regional fat and insulin sensitivity and compared the effect of total energy expenditure from all levels of physical activity with that of physical activity energy expenditure from moderate-to-vigorous exercise in obese women with Type 2 diabetes . METHODS In this r and omized , controlled trial , we assessed change of body weight , abdominal visceral fat area , subcutaneous fat area and insulin sensitivity , expressed as K(ITT ) , and monitored total energy expenditure and physical activity energy expenditure using an accelerometer during a 12-week intervention in four groups : control , diet , exercise and diet plus exercise . RESULTS The mean body mass index was 28.0 + /- 2.7 kg/m(2 ) and the mean duration of diabetes was 8 + /- 6 years . Both the diet and diet plus exercise groups showed significant body weight loss compared with the control group ( P < 0.05 ) . However , the visceral fat area was reduced only in the diet and exercise group ( P = 0.017 ) and the subcutaneous fat area was reduced only in the diet group ( P = 0.009 ) . Mean energy intake was an independent determinant of the change in subcutaneous fat area ( P = 0.020 ) and mean total anergy expenditure was an independent determinant of visceral fat area ( P = 0.002 ) . Insulin sensitivity K(ITT ) was associated with physical activity energy expenditure ( P = 0.006 ) , energy intake ( P = 0.047 ) and the change in fructosamine level ( P = 0.016 ) but not with changes in body weight , subcutaneous fat area , visceral fat area or adipokine level . CONCLUSIONS Exercise had an additive effect to dietary restriction on visceral fat reduction . Visceral fat area was associated with total energy expenditure , but insulin sensitivity was associated with physical activity energy expenditure BACKGROUND & AIMS We determined the effects of acute and chronic calorie restriction with either a low-fat , high-carbohydrate ( HC ) diet or a low-carbohydrate ( LC ) diet on hepatic and skeletal muscle insulin sensitivity . METHODS Twenty-two obese subjects ( body mass index , 36.5 + /- 0.8 kg/m2 ) were r and omized to an HC ( > 180 g/day ) or LC ( < 50 g/day ) energy-deficit diet . A euglycemic-hyperinsulinemic clamp , muscle biopsy specimens , and magnetic resonance spectroscopy were used to determine insulin action , cellular insulin signaling , and intrahepatic triglyceride ( IHTG ) content before , after 48 hours , and after approximately 11 weeks ( 7 % weight loss ) of diet therapy . RESULTS At 48 hours , IHTG content decreased more in the LC than the HC diet group ( 29.6 % + /- 4.8 % vs 8.9 % + /- 1.4 % ; P < .05 ) but was similar in both groups after 7 % weight loss ( LC diet , 38.0 % + /- 4.5 % ; HC diet , 44.5 % + /- 13.5 % ) . Basal glucose production rate decreased more in the LC than the HC diet group at 48 hours ( 23.4 % + /- 2.2 % vs 7.2 % + /- 1.4 % ; P < .05 ) and after 7 % weight loss ( 20.0 % + /- 2.4 % vs 7.9 % + /- 1.2 % ; P < .05 ) . Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7 % weight loss ( 48.4 % + /- 14.3 % ; P < .05 ) . In both groups , insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29 % + /- 13 % and phosphorylation of Akt and insulin receptor substrate 1 increased by 35 % + /- 9 % and 36 % + /- 9 % , respectively , after 7 % weight loss ( all P < .05 ) . CONCLUSIONS Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism ; 48 hours of calorie restriction affects the liver ( IHTG content , hepatic insulin sensitivity , and glucose production ) , whereas moderate weight loss affects muscle ( insulin-mediated glucose uptake and insulin signaling ) BACKGROUND & AIMS Despite increasing use of various imaging examinations for non-invasive assessment of hepatic steatosis ( HS ) , their relative accuracy is unknown . The objective of this study is to prospect ively compare the accuracy of computed tomography ( CT ) , dual gradient echo magnetic resonance imaging ( DGE-MRI ) , proton magnetic resonance spectroscopy ( (1)H-MRS ) , and ultrasonography ( US ) for the diagnosis and quantitative estimation of HS . METHODS A total of 161 consecutive potential living liver donors underwent US ( performed by two independent radiologists , US1 and US2 ) , CT , DGE-MRI , (1)H-MRS , and liver biopsy on the same day . Using the histologic degree of HS as the reference st and ard , we compared the diagnostic performance of US1 , US2 , CT , DGE-MRI , and (1)H-MRS for diagnosing HS > or= 5 % and HS > or= 30 % and compared the accuracy of CT , DGE-MRI , and (1)H-MRS in the quantitative estimation of HS . RESULTS  DGE-MRI and (1)H-MRS  significantly outperformed CT and US for the diagnosis of HS5 % .  DGE-MRI  showed a tendency of higher accuracy than the other examinations for diagnosing HS > or= 30 % . The cross-vali date d sensitivity and specificity of DGE-MRI  at the optimal cut-off were 76.7 % and 87.1 % , respectively , for diagnosing HS > or= 5 % and 90.9 % and 94 % , respectively , for diagnosing HS > or= 30 % . The cross-vali date d Bl and -Altman 95 % limits of agreement between the estimated degree of HS on imaging examinations and the histologic degree of HS , were the narrowest with DGE-MRI , yielding -12.7 % to 12.7 % . CONCLUSIONS Among CT , DGE-MRI , (1)H-MRS , and US , DGE-MRI is the most accurate method for the diagnosis and quantitative estimation of HS . Therefore , DGE-MRI may be the preferred imaging examination for the non-invasive assessment of HS Despite the increasing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , the criteria used to diagnose the disorder remain poorly defined . Localized proton magnetic resonance spectroscopy ( MRS ) accurately measures hepatic triglyceride content ( HTGC ) but has been used only in small research studies . Here , MRS was used to analyze the distribution of HTGC in 2,349 participants from the Dallas Heart Study ( DHS ) . The reproducibility of the procedure was vali date d by showing that duplicate HTGC measurements were high correlated ( r = 0.99 , P < 0.001 ) and that the coefficient of variation between measurements was low ( 8.5 % ) . Intake of a high-fat meal did not significantly affect the measurements , and values were similar when measurements were made from the right and left hepatic lobes . To determine the " upper limit of normal " for HTGC , the distribution of HTGC was examined in the 345 subjects from the DHS who had no identifiable risk factors for hepatic steatosis ( nonobese , nondiabetic subjects with minimal alcohol consumption , normal liver function tests , and no known liver disease ) . The 95th percentile of HTGC in these subjects was 5.56 % , which corresponds to a hepatic triglyceride level of 55.6 mg/g . With this value as a cutoff , the prevalence of hepatic steatosis in Dallas County was estimated to be 33.6 % . Thus MRS provides a sensitive , quantitative , noninvasive method to measure HTGC and , when applied to a large urban US population , revealed a strikingly high prevalence of hepatic steatosis OBJECTIVE Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes , and conjunctive use of weight loss medication has been advocated . The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment , using behavioral intervention ( Int ) combined with r and omized , double-blinded , placebo (P)-controlled treatment with orlistat ( O ) . RESEARCH DESIGN AND METHODS Metabolic control , insulin sensitivity ( IS ) , regional fat distribution , and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding r and omization .  Weight loss was equivalent in the Int+O and Int+P groups , respectively ( -10.3 + /- 1.3 vs. -8.9 + /- 1.1 % ) , and there were identical decreases in visceral adipose tissue ( VAT ) , fat mass ( FM ) , thigh adiposity , and hepatic steatosis . RESULTS Weight loss result ed in substantial improvement ( P < 0.001 ) in HbA(1c ) ( -1.6 + /- 0.3 vs. -1.0 + /- 0.4 % ; NS between groups ) . IS improved significantly more with orlistat ( Delta2.2 + /- 0.4 vs. Delta1.2 + /- 0.4 mg . min(-1 ) . kg(-1 ) fat-free mass [ FFM ] ; P < 0.05 ) , and plasma free fatty acid ( FFA ) levels were strongly correlated with IS ( r = 0.56 ; P < 0.001 ) . Orlistat caused greater reductions in fasting plasma FFA ( Delta-154 + /- 22 vs. Delta-51 + /- 33 micro mol/l ; P < 0.05 ) , insulin-suppressed FFA ( Delta-119 + /- 23 vs. Delta-87 + /- 34 micro mol/l ; P < 0.05 ) , and fasting plasma glucose ( FPG ; -62 + /- 9 vs. -32 + /- 8 mg/dl ; P = 0.02 ) . Changes in HbA(1c ) were correlated with DeltaIS ( r = -0.41 ; P < 0.01 ) but not with weight loss per se . CONCLUSIONS At equivalent weight loss , conjunctive use of orlistat result ed in greater improvement in FFA levels and IS OBJECTIVE Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease ( NAFLD ) . However , its efficacy in patients with type 2 diabetes is unproven . RESEARCH DESIGN AND METHODS Look AHEAD ( Action for Health in Diabetes ) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes , who were r and omly assigned to an intensive lifestyle intervention ( ILI )  to induce a minimum weight loss of 7 % or a control group who received diabetes support and education ( DSE ) . In the Fatty Liver Ancillary Study , 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months . We defined steatosis > 5.5 % as NAFLD . RESULTS Participants were 49 % women and 68 % white . The mean age was 61 years , mean BMI was 35 kg/m2 , mean steatosis was 8.0 % , and mean aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) were 20.5 and 24.2 units/l , respectively . After 12 months , participants assigned to ILI ( n = 46 ) lost more weight ( −8.5 vs. −0.05 % ; P < 0.01 ) than those assigned to DSE and had a greater decline in steatosis ( −50.8 vs. −22.8 % ; P = 0.04 ) and in A1C ( −0.7 vs. −0.2 % ; P = 0.04 ) . There were no significant 12-month changes in AST or ALT levels . At 12 months , 26 % of DSE participants and 3 % ( 1 of 31 ) of ILI participants without NAFLD at baseline developed NAFLD ( P < 0.05 ) . CONCLUSIONS A 12-month intensive lifestyle intervention in patients with type 2 diabetes  reduces steatosis and incident NAFLD To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes , we used (1)H magnetic resonance spectroscopy to assess intrahepatic lipid ( IHL ) and intramyocellular lipid ( IMCL ) content in conjunction with hyperinsulinemic-euglycemic clamps using [6,6-(2)H(2)]glucose to assess 
    Output:
    