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: OBJECTIVE —Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks . However , prospect i ve data using the biomarker serum 25-hydroxyvitamin D [ 25(OH)D ] are limited and therefore examined in the present study . RESEARCH DESIGN AND METHODS —A total of 524 r and omly selected nondiabetic men and women , aged 40–69 years at baseline , with measurements for serum 25(OH)D and IGF-1 in the population -based Ely Study , had glycemic status ( oral glucose tolerance ) , lipids , insulin , anthropometry , and blood pressure measured and metabolic syndrome risk ( metabolic syndrome z score ) derived at baseline and at 10 years of follow-up . RESULTS —Age-adjusted baseline mean serum 25(OH)D was greater in men ( 64.5 nmol/l [ 95 % CI 61.2–67.9 ] ) than women ( 57.2 nmol/l [ 54.4,60.0 ] ) and varied with season ( highest late summer ) . Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia ( fasting glucose : β = −0.0023 , P = 0.019 ; 2-h glucose : β = −0.0097 , P = 0.006 ) , insulin resistance ( fasting insulin β = −0.1467 , P = 0.010 ; homeostasis model assessment of insulin resistance [ HOMA-IR ] : β = −0.0059 , P = 0.005 ) , and metabolic syndrome z score ( β = −0.0016 , P = 0.048 ) after adjustment for age , sex , smoking , BMI , season , and baseline value of each metabolic outcome variable . Associations with 2-h glucose , insulin , and HOMA-IR remained significant after further adjustment for IGF-1 , parathyroid hormone , calcium , physical activity , and social class . CONCLUSIONS —This prospect i ve study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance . These associations are potentially important in underst and ing the etiology of abnormal glucose metabolism and warrant investigation in larger , specifically design ed prospect i ve studies and r and omized controlled trials of supplementation OBJECTIVE Low vitamin D levels predict the development of diabetes . This double-blind , r and omized , control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion , insulin sensitivity , and the development of diabetes . RESEARCH DESIGN AND METHODS A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels . Subjects with A1C levels of 5.8–6.9 % underwent an oral glucose tolerance test ( OGTT ) . Subjects with prediabetes and 25-OH vitamin D ( 25-OHD ) levels < 30 ng/mL were r and omized to receive weekly placebo ( n = 53 ) or vitamin D ( n = 56 ) with doses based on body weight and baseline 25-OHD levels . OGTTs were performed 3 , 6 , 9 , and 12 months later . Insulin secretion and sensitivity were measured , and the proportion of subjects developing diabetes was assessed . RESULTS 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU . There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose , 2-h glucose , or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance . No subjects experienced increased serum or urinary calcium levels . At 12 months , A1C levels were significantly slightly less ( 0.2 % ) in the vitamin D group . CONCLUSIONS In individuals with prediabetes and hypovitaminosis D , doses of vitamin D supplementation design ed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion , insulin sensitivity , or the development of diabetes  compared with placebo administration BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events OBJECTIVE The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume , serum TNF-alpha , soluble TNF-receptor-2 ( sTNFR-2 ) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons . DESIGN A cross-sectional case-control study was used . PATIENTS Twenty-eight overweight/obese prob and s with normal glucose tolerance ( BMI > 27 kg/m(2 ) ) and 15 lean people ( BMI < 25 kg/m(2 ) ) , all of them undergoing planned surgical operation , participated in the study . METHODS Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein . Serum TNF-alpha , sTNFR-2 ( ELISA ) and fasting C-peptide ( RIA )  were measured . RESULTS TNF-alpha protein was expressed in adipocytes of both depots . The expression was evaluated visually and found to be greater in the obese patients . Significantly higher serum TNF-alpha ( 5.58+/-0.87 pg/ml vs 4.21+/-0.55 , mean+/-s.d . , P<0.01 , Mann-Whitney ) and sTNFR-2 levels ( 7.84+/-3.56 ng/ml vs 4.59+/-1.35 , P=0.005 ) were found in the obese subgroup in correlation with the fasting C-peptide level ( r=0.49 , P=0.003 ; and r=0.74 , P=0.001 ) and the C-peptide/ blood glucose ratio ( r=0.47 , Spearman , P=0.005 ; and r=0.70 , P=0.001 ) . The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients ( subcutaneous : r=0.52 , P=0.0003 ; r=0.69 , P<0.0001 ; visceral : r=0.65 , P<0.0001 ; r=0.63 , P<0.0001 ) and in both subgroups . CONCLUSIONS Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha , sTNFR-2 production and obesity-linked insulin resistance The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [ 25(OH)D ] and high-density lipoprotein cholesterol ( HDL-C ) in subjects with high waist circumference . Subjects were r and omly assigned a daily multivitamin and mineral ( MVM ) supplement or a MVM supplement plus vitamin D 1,200 IU/day ( MVM+D ) for 8 weeks . There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( − 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l , respectively ; P = 0.003 ) . Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l ) in 61 % of participants . There were no significant changes in cardiovascular disease risk markers . Thus , vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers Background Recent evidence suggests that higher calcium and /or vitamin D intake may be associated with lower body weight and better metabolic health . Due to contradictory findings from intervention trials , we investigated the effect of calcium plus vitamin D3 ( calcium+D ) supplementation on anthropometric and metabolic profiles during energy restriction in healthy , overweight and obese adults with very-low calcium consumption . Methods Fifty-three subjects were r and omly assigned in an open-label , r and omized controlled trial to receive either an energy-restricted diet ( −500 kcal/d ) supplemented with 600 mg elemental calcium and 125 IU vitamin D3 or energy restriction alone for 12 weeks . Repeated measurements of variance were performed to evaluate the differences between groups for changes in body weight , BMI , body composition , waist circumference , and blood pressures , as well as in plasma TG , TC , HDL , LDL , glucose and insulin concentrations . Results Eighty-one percent of participants completed the trial ( 85 % from the calcium + D group ; 78 % from the control group ) . A significantly greater decrease in fat mass loss was observed in the calcium + D group ( −2.8±1.3 vs.-1.8±1.3 kg ; P=0.02 ) than in the control group , although there was no significant difference in body weight change ( P>0.05 ) between groups . The calcium + D group also exhibited greater decrease in visceral fat mass and visceral fat area ( P<0.05 for both ) . No significant difference was detected for changes in metabolic variables ( P>0.05 ) . Conclusion Calcium plus vitamin D3 supplementation for 12 weeks augmented body fat and visceral fat loss in very-low calcium consumers during energy restriction . Trial registration Clinical Trials.gov ( NCT01447433 , http:// clinical trials.gov/ ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The purpose of this study was to examine the effects of vitamin D supplementation on inflammatory biomarkers in overweight and obese adults participating in a progressive resistance exercise training program . Twenty-three ( 26.1 
    Output:
    
agent
Baseline serum VD possibly influences the effect of VD repletion on inflammatory markers .
Risk of bias was present in most studies , thus supporting the need for higher quality studies in this area to more conclusively underst and the role VD supplementation has on inflammatory pathways
***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: OBJECTIVE —Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks . However , prospect i ve data using the biomarker serum 25-hydroxyvitamin D [ 25(OH)D ] are limited and therefore examined in the present study . RESEARCH DESIGN AND METHODS —A total of 524 r and omly selected nondiabetic men and women , aged 40–69 years at baseline , with measurements for serum 25(OH)D and IGF-1 in the population -based Ely Study , had glycemic status ( oral glucose tolerance ) , lipids , insulin , anthropometry , and blood pressure measured and metabolic syndrome risk ( metabolic syndrome z score ) derived at baseline and at 10 years of follow-up . RESULTS —Age-adjusted baseline mean serum 25(OH)D was greater in men ( 64.5 nmol/l [ 95 % CI 61.2–67.9 ] ) than women ( 57.2 nmol/l [ 54.4,60.0 ] ) and varied with season ( highest late summer ) . Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia ( fasting glucose : β = −0.0023 , P = 0.019 ; 2-h glucose : β = −0.0097 , P = 0.006 ) , insulin resistance ( fasting insulin β = −0.1467 , P = 0.010 ; homeostasis model assessment of insulin resistance [ HOMA-IR ] : β = −0.0059 , P = 0.005 ) , and metabolic syndrome z score ( β = −0.0016 , P = 0.048 ) after adjustment for age , sex , smoking , BMI , season , and baseline value of each metabolic outcome variable . Associations with 2-h glucose , insulin , and HOMA-IR remained significant after further adjustment for IGF-1 , parathyroid hormone , calcium , physical activity , and social class . CONCLUSIONS —This prospect i ve study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance . These associations are potentially important in underst and ing the etiology of abnormal glucose metabolism and warrant investigation in larger , specifically design ed prospect i ve studies and r and omized controlled trials of supplementation OBJECTIVE Low vitamin D levels predict the development of diabetes . This double-blind , r and omized , control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion , insulin sensitivity , and the development of diabetes . RESEARCH DESIGN AND METHODS A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels . Subjects with A1C levels of 5.8–6.9 % underwent an oral glucose tolerance test ( OGTT ) . Subjects with prediabetes and 25-OH vitamin D ( 25-OHD ) levels < 30 ng/mL were r and omized to receive weekly placebo ( n = 53 ) or vitamin D ( n = 56 ) with doses based on body weight and baseline 25-OHD levels . OGTTs were performed 3 , 6 , 9 , and 12 months later . Insulin secretion and sensitivity were measured , and the proportion of subjects developing diabetes was assessed . RESULTS 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU . There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose , 2-h glucose , or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance . No subjects experienced increased serum or urinary calcium levels . At 12 months , A1C levels were significantly slightly less ( 0.2 % ) in the vitamin D group . CONCLUSIONS In individuals with prediabetes and hypovitaminosis D , doses of vitamin D supplementation design ed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion , insulin sensitivity , or the development of diabetes  compared with placebo administration BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events OBJECTIVE The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume , serum TNF-alpha , soluble TNF-receptor-2 ( sTNFR-2 ) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons . DESIGN A cross-sectional case-control study was used . PATIENTS Twenty-eight overweight/obese prob and s with normal glucose tolerance ( BMI > 27 kg/m(2 ) ) and 15 lean people ( BMI < 25 kg/m(2 ) ) , all of them undergoing planned surgical operation , participated in the study . METHODS Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein . Serum TNF-alpha , sTNFR-2 ( ELISA ) and fasting C-peptide ( RIA )  were measured . RESULTS TNF-alpha protein was expressed in adipocytes of both depots . The expression was evaluated visually and found to be greater in the obese patients . Significantly higher serum TNF-alpha ( 5.58+/-0.87 pg/ml vs 4.21+/-0.55 , mean+/-s.d . , P<0.01 , Mann-Whitney ) and sTNFR-2 levels ( 7.84+/-3.56 ng/ml vs 4.59+/-1.35 , P=0.005 ) were found in the obese subgroup in correlation with the fasting C-peptide level ( r=0.49 , P=0.003 ; and r=0.74 , P=0.001 ) and the C-peptide/ blood glucose ratio ( r=0.47 , Spearman , P=0.005 ; and r=0.70 , P=0.001 ) . The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients ( subcutaneous : r=0.52 , P=0.0003 ; r=0.69 , P<0.0001 ; visceral : r=0.65 , P<0.0001 ; r=0.63 , P<0.0001 ) and in both subgroups . CONCLUSIONS Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha , sTNFR-2 production and obesity-linked insulin resistance The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [ 25(OH)D ] and high-density lipoprotein cholesterol ( HDL-C ) in subjects with high waist circumference . Subjects were r and omly assigned a daily multivitamin and mineral ( MVM ) supplement or a MVM supplement plus vitamin D 1,200 IU/day ( MVM+D ) for 8 weeks . There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( − 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l , respectively ; P = 0.003 ) . Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l ) in 61 % of participants . There were no significant changes in cardiovascular disease risk markers . Thus , vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers Background Recent evidence suggests that higher calcium and /or vitamin D intake may be associated with lower body weight and better metabolic health . Due to contradictory findings from intervention trials , we investigated the effect of calcium plus vitamin D3 ( calcium+D ) supplementation on anthropometric and metabolic profiles during energy restriction in healthy , overweight and obese adults with very-low calcium consumption . Methods Fifty-three subjects were r and omly assigned in an open-label , r and omized controlled trial to receive either an energy-restricted diet ( −500 kcal/d ) supplemented with 600 mg elemental calcium and 125 IU vitamin D3 or energy restriction alone for 12 weeks . Repeated measurements of variance were performed to evaluate the differences between groups for changes in body weight , BMI , body composition , waist circumference , and blood pressures , as well as in plasma TG , TC , HDL , LDL , glucose and insulin concentrations . Results Eighty-one percent of participants completed the trial ( 85 % from the calcium + D group ; 78 % from the control group ) . A significantly greater decrease in fat mass loss was observed in the calcium + D group ( −2.8±1.3 vs.-1.8±1.3 kg ; P=0.02 ) than in the control group , although there was no significant difference in body weight change ( P>0.05 ) between groups . The calcium + D group also exhibited greater decrease in visceral fat mass and visceral fat area ( P<0.05 for both ) . No significant difference was detected for changes in metabolic variables ( P>0.05 ) . Conclusion Calcium plus vitamin D3 supplementation for 12 weeks augmented body fat and visceral fat loss in very-low calcium consumers during energy restriction . Trial registration Clinical Trials.gov ( NCT01447433 , http:// clinical trials.gov/ ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The purpose of this study was to examine the effects of vitamin D supplementation on inflammatory biomarkers in overweight and obese adults participating in a progressive resistance exercise training program . Twenty-three ( 26.1 
    Output:
    