the strong heart study ( shs ) is a multicenter , population - based , prospective study of cardiovascular disease ( cvd ) and its risk factors among ai adults . the study design , survey methods , and laboratory techniques have been described previously ( 11,12 ) . the present analysis was based on the second examination and the 4-year follow - up clinic visit  the third examination . approval was obtained from relevant institutional review boards , and all participants gave written informed consent . the following criteria were used in excluding participants from the analysis population : 1 ) > 20 pack - year smoking history ( n = 639 ) , 2 ) any self - reported lung problems and taking asthma medications ( n = 179 ) , 3 ) having cvd ( n = 430 ) , and 4 ) missing data on dm , ms status , or spirometry ( n = 268 ) . the final study sample consisted of 2,396 individuals , including 483 adults without ms or dm ( normal group ) , 729 adults without dm and with ms ( ms group ) , and 1,184 adults with dm ( dm group ) at the second examination . ms - free ( 483 normal ) and dm - free ( 483 normal and 729 ms ) participants were used for the prediction of ms and dm , respectively . normal reference values for the pulmonary function test ( pft ) were derived from the shs population ; shs - specific forced vital capacity ( fvc ) and forced expiratory volume in 1 s ( fev1 ) were predicted using the equations developed by marion et al . ( 13 ) for healthy shs participants using the covariates of age , sex , and height . the prediction equations for normal lung function for men are as follows : the prediction equations for normal lung function for women are as follows : before the analysis , crude data on fvc and fev1 were divided by predicted fvc and fev1 , respectively , to yield fvc % predicted and fev1 % predicted . individuals were classified as having dm according to the 1997 american diabetes association criteria ; a fasting glucose level of at least 7.0 mmol / l ( 126 mg / dl ) ; current use of antidiabetes medication ; or on renal dialysis / kidney transplant with a positive response to the question ,  has a medical person ever told you that you had diabetes ?  this group included both t1 dm and t2 dm ; the majority of the participants were t2 dm . ms was defined according to the third report of the national cholesterol education program expert panel on detection , evaluation , and treatment of high blood cholesterol in adults ( adult treatment panel iii ) guidelines ( 14 ) as having at least three of the following five conditions : abdominal obesity ( waist circumference [ wc ] > 102 cm in men and > 88 cm in women ) , increased triglycerides ( 150 mg / dl ) , reduced hdl cholesterol ( < 40 mg / dl in men and < 50 mg / dl in women ) , elevated blood pressure ( 130/85 mmhg ) , and high fasting glucose ( 100125 mg / dl ) . the definitions and methods used for other measurements ( age , education level , cigarette smoking status and pack - years of smoking , physical activity index , height , bmi , and hypertension ) have been reported previously ( 12,15 ) . the methods used for the measurement of fibrinogen and c - reactive protein ( crp ) were also reported before ( 16 ) . the homeostasis model assessment for insulin resistance ( homa - ir ) was calculated according to the following formula : ( fasting insulin in u / ml  fasting glucose in mg / dl)/405 . characteristics of normal , ms , and dm groups were compared using anova for continuous variables and  tests for categorical variables . kruskal - wallis anova by ranks was used to compare total triglycerides , plasminogen activator inhibitor-1 , and crp because of skewed distributions . multiple linear regression models were used to describe the cross - sectional relationships between lung function and metabolic disorders ( ms and dm ) after adjusting for potential confounding variables including age , sex , abdominal obesity , height , hypertension , physical activity index , education level , current smoking status , and shs center . the same models were also fitted to describe the cross - sectional associations among lung function and duration of dm , type of antidiabetes medications , and tertiles of insulin resistance after adjusting for potential confounding variables . multiple linear regression models were also used to describe the cross - sectional relationships between lung function and inflammatory markers ( crp and fibrinogen ) . for crp analyses , participants with values > 10 mg / l were excluded because crp levels > 10 mg / l may reflect an acute inflammatory process ; crp > 3 mg / l was used as the high crp cut point based on the american heart association / centers for disease control and prevention categories ( 17 ) . for fibrinogen analyses , the lowest tertile of fibrinogen level in the normal group ( 350 mg / dl ) was used as a control for the lung function comparisons . multiple linear regression models were also carried out for investigation of the cross - sectional relationship between lung function and obesity . cox proportional hazards models were used to analyze the association between dm / ms and pulmonary function , controlling for confounding variables . all analyses were performed using version 9.1 of the sas statistical software package ( sas institute , cary , nc ) . normal reference values for the pulmonary function test ( pft ) were derived from the shs population ; shs - specific forced vital capacity ( fvc ) and forced expiratory volume in 1 s ( fev1 ) were predicted using the equations developed by marion et al . ( 13 ) for healthy shs participants using the covariates of age , sex , and height . the prediction equations for normal lung function for men are as follows : the prediction equations for normal lung function for women are as follows : before the analysis , crude data on fvc and fev1 were divided by predicted fvc and fev1 , respectively , to yield fvc % predicted and fev1 % predicted . individuals were classified as having dm according to the 1997 american diabetes association criteria ; a fasting glucose level of at least 7.0 mmol / l ( 126 mg / dl ) ; current use of antidiabetes medication ; or on renal dialysis / kidney transplant with a positive response to the question ,  has a medical person ever told you that you had diabetes ?  this group included both t1 dm and t2 dm ; the majority of the participants were t2 dm . ms was defined according to the third report of the national cholesterol education program expert panel on detection , evaluation , and treatment of high blood cholesterol in adults ( adult treatment panel iii ) guidelines ( 14 ) as having at least three of the following five conditions : abdominal obesity ( waist circumference [ wc ] > 102 cm in men and > 88 cm in women ) , increased triglycerides ( 150 mg / dl ) , reduced hdl cholesterol ( < 40 mg / dl in men and < 50 mg / dl in women ) , elevated blood pressure ( 130/85 mmhg ) , and high fasting glucose ( 100125 mg / dl ) . the definitions and methods used for other measurements ( age , education level , cigarette smoking status and pack - years of smoking , physical activity index , height , bmi , and hypertension ) have been reported previously ( 12,15 ) . the methods used for the measurement of fibrinogen and c - reactive protein ( crp ) were also reported before ( 16 ) . the homeostasis model assessment for insulin resistance ( homa - ir ) was calculated according to the following formula : ( fasting insulin in u / ml  fasting glucose in mg / dl)/405 . characteristics of normal , ms , and dm groups were compared using anova for continuous variables and  tests for categorical variables . kruskal - wallis anova by ranks was used to compare total triglycerides , plasminogen activator inhibitor-1 , and crp because of skewed distributions . multiple linear regression models were used to describe the cross - sectional relationships between lung function and metabolic disorders ( ms and dm ) after adjusting for potential confounding variables including age , sex , abdominal obesity , height , hypertension , physical activity index , education level , current smoking status , and shs center . the same models were also fitted to describe the cross - sectional associations among lung function and duration of dm , type of antidiabetes medications , and tertiles of insulin resistance after adjusting for potential confounding variables . multiple linear regression models were also used to describe the cross - sectional relationships between lung function and inflammatory markers ( crp and fibrinogen ) . for crp analyses , participants with values > 10 mg / l were excluded because crp levels > 10 mg / l may reflect an acute inflammatory process ; crp > 3 mg / l was used as the high crp cut point based on the american heart association / centers for disease control and prevention categories ( 17 ) . for fibrinogen analyses , the lowest tertile of fibrinogen level in the normal group ( 350 mg / dl ) was used as a control for the lung function comparisons . multiple linear regression models were also carried out for investigation of the cross - sectional relationship between lung function and obesity . cox proportional hazards models were used to analyze the association between dm / ms and pulmonary function , controlling for confounding variables . all analyses were performed using version 9.1 of the sas statistical software package ( sas institute , cary , nc ) . characteristics of the three groups ( normal , ms , and dm ) are summarized in table 1 . of the participants , 75.2% reported 100% ai heritage . in general , participants with dm or ms were more likely to be hypertensive and smoked less than the normal group . they were also more likely to have a larger wc , higher triglycerides , lower hdl cholesterol , higher hemoglobin a1c , presence of albuminuria , and an elevated concentration of inflammatory markers compared with the normal group . ldl cholesterol was higher in the ms group than in the normal and dm groups . demographic information for normal , ms , and dm groups data in parentheses are 1 sd for continuous variables and 95% ci for percentages unless otherwise indicated * for continuous variables , analyses of variance were used to calculate the p values ; for categorical variables ,  tests were used to calculate the p values . for the clinical measurements of the excluded group because of missing dm , ms , or pft status were similar to those of the study group , with the exception that they were more likely to have smaller wcs ( data not shown ) . both percent predicted values for fvc and fev1 were significantly lower in the participants with ms or dm compared with their normal counterparts ( p < 0.0001 ) ( table 1 ) , even after adjusting for age , sex , abdominal obesity , height , hypertension , sports activity index , education level , current smoking status , and shs center ( table 2 ) . an increased trend for ms and dm was observed for the fev1-to - fvc ratio . adjusted spirometry results for normal , ms , and dm groups and by insulin resistance and dm severity data are means ( 95% ci ) adjusted for age , sex , abdominal obesity , height , hypertension , physical activity index , education level , current smoking status , and shs center . significant relationships were found among pulmonary function and insulin resistance , duration of dm , and antidiabetes medications . participants with higher homa - ir scores had greater reductions in both predicted fvc and fev1 values ( ptrend < 0.05 ) ( table 2 ) . subdividing the participants by duration of dm revealed that absolute and percent predicted fvc decreased with duration of dm ( ptrend < 0.01 ) . however , the reductions of fev1 values were not different for durations < 5 years vs. > 10 years . subdividing the participants by antidiabetes medications revealed that pulmonary function was significantly reduced in participants requiring insulin treatment compared with those on oral agents alone or no medication ( ptrend < 0.01 ) . the relatively greater reduction in fvc than in fev1 in dm participants with longer duration or more severe dm partitioning normal , ms , and dm participants according to blood levels of the inflammatory markers crp and fibrinogen revealed that pulmonary function decreased as marker concentration increased ( table 3 ) . compared with normal participants , ms and dm groups with elevated inflammatory markers had greater reductions in their pft ( fvc , fev1 , fvc % predicted , and fev1 % predicted all ptrend < 0.01 ) . adjusted spirometry results for normal , ms , and dm groups by inflammatory markers data are means ( 95% ci ) adjusted for age , sex , height , hypertension , physical activity index , education level , current smoking status , and shs center . high fibrinogen was defined as plasma fibrinogen > 350 mg / dl . among 1,212 participants who were dm - free at the shs second examination , 129 developed dm during the 4 years of follow - up . by use of cox proportional hazards models , in unadjusted analyses with fvc , fvc % predicted , fev1 , fev1 % predicted , and fev1-to - fvc ratio as continuous independent variables , fvc % predicted and fev1-to - fvc ratio both predicted dm ( table 4 , model 2 ) . the risk of incident dm increased 3% for every 1% increase in fev1-to - fvc ratio ( hazard ratio 1.03 [ 95% ci 1.011.06 ] ) , and the risk of incident dm increased 2% for every 1% decrease in fvc % predicted ( 0.98 [ 0.970.99 ] ) . the same results were obtained when age , sex , and shs center were added to the model as covariates ( model 3 ) . however , when more covariates ( abdominal obesity , hypertension , physical activity index , education level , and pack - years of smoking ) were added to the cox proportional hazards model , pulmonary function did not predict dm ( table 4 , model 4 ) ; abdominal obesity , as measured by wc , was retained in the final model as an independent predictor of the development of dm . cox proportional hazards models for the prediction of dm or ms based on pfts * the model was reduced by stepwise selection . all covariates were candidates for removal . only those covariates that remained significant ( p  0.05 ) are shown in the table . the covariates considered in the model were age , sex , abdominal obesity , hypertension , per pack - year smoking , physical activity index , education level , and shs center . only those covariates that remained significant ( p  0.05 ) are shown in the table . similar analyses of data from participants who developed ms indicated that fev1-to - fvc ratio predicted dm ; however , neither fvc nor fev1 alone predicted this syndrome . as before , abdominal obesity was retained in the final model as an independent predictor for ms ( table 4 ) . further investigation of obesity showed a significant reduction in pulmonary function in obese participants measured either by wc or by bmi ( table 5 ) . compared with normal participants , ms and dm adults with obesity had greater reductions in their pft ( fvc , fev1 , fvc % predicted , and fev1 % predicted all ptrend < 0.05 ) . adjusted spirometry results for normal , ms , and dm groups by obesity status data are means ( 95% ci ) adjusted for age , sex , height , hypertension , physical activity index , education level , current smoking status , and shs center . * ao was defined as wc > 102 cm in men and > 88 cm in women . characteristics of the three groups ( normal , ms , and dm ) are summarized in table 1 . of the participants , 75.2% reported 100% ai heritage . in general , participants with dm or ms were more likely to be hypertensive and smoked less than the normal group . they were also more likely to have a larger wc , higher triglycerides , lower hdl cholesterol , higher hemoglobin a1c , presence of albuminuria , and an elevated concentration of inflammatory markers compared with the normal group . ldl cholesterol was higher in the ms group than in the normal and dm groups . demographic information for normal , ms , and dm groups data in parentheses are 1 sd for continuous variables and 95% ci for percentages unless otherwise indicated * for continuous variables , analyses of variance were used to calculate the p values ; for categorical variables ,  tests were used to calculate the p values . for the clinical measurements of the excluded group because of missing dm , ms , or pft status were similar to those of the study group , with the exception that they were more likely to have smaller wcs ( data not shown ) . both percent predicted values for fvc and fev1 were significantly lower in the participants with ms or dm compared with their normal counterparts ( p < 0.0001 ) ( table 1 ) , even after adjusting for age , sex , abdominal obesity , height , hypertension , sports activity index , education level , current smoking status , and shs center ( table 2 ) . an increased trend for ms and dm was observed for the fev1-to - fvc ratio . adjusted spirometry results for normal , ms , and dm groups and by insulin resistance and dm severity data are means ( 95% ci ) adjusted for age , sex , abdominal obesity , height , hypertension , physical activity index , education level , current smoking status , and shs center . significant relationships were found among pulmonary function and insulin resistance , duration of dm , and antidiabetes medications . participants with higher homa - ir scores had greater reductions in both predicted fvc and fev1 values ( ptrend < 0.05 ) ( table 2 ) . subdividing the participants by duration of dm revealed that absolute and percent predicted fvc decreased with duration of dm ( ptrend < 0.01 ) . however , the reductions of fev1 values were not different for durations < 5 years vs. > 10 years . subdividing the participants by antidiabetes medications revealed that pulmonary function was significantly reduced in participants requiring insulin treatment compared with those on oral agents alone or no medication ( ptrend < 0.01 ) . the relatively greater reduction in fvc than in fev1 in dm participants with longer duration or more severe dm was reflected in the fev1-to - fvc ratio . partitioning normal , ms , and dm participants according to blood levels of the inflammatory markers crp and fibrinogen revealed that pulmonary function decreased as marker concentration increased ( table 3 ) . compared with normal participants , ms and dm groups with elevated inflammatory markers had greater reductions in their pft ( fvc , fev1 , fvc % predicted , and fev1 % predicted all ptrend < 0.01 ) . adjusted spirometry results for normal , ms , and dm groups by inflammatory markers data are means ( 95% ci ) adjusted for age , sex , height , hypertension , physical activity index , education level , current smoking status , and shs center . among 1,212 participants who were dm - free at the shs second examination , 129 developed dm during the 4 years of follow - up . by use of cox proportional hazards models , in unadjusted analyses with fvc , fvc % predicted , fev1 , fev1 % predicted , and fev1-to - fvc ratio as continuous independent variables , fvc % predicted and fev1-to - fvc ratio both predicted dm ( table 4 , model 2 ) . the risk of incident dm increased 3% for every 1% increase in fev1-to - fvc ratio ( hazard ratio 1.03 [ 95% ci 1.011.06 ] ) , and the risk of incident dm increased 2% for every 1% decrease in fvc % predicted ( 0.98 [ 0.970.99 ] ) . the same results were obtained when age , sex , and shs center were added to the model as covariates ( model 3 ) . however , when more covariates ( abdominal obesity , hypertension , physical activity index , education level , and pack - years of smoking ) were added to the cox proportional hazards model , pulmonary function did not predict dm ( table 4 , model 4 ) ; abdominal obesity , as measured by wc , was retained in the final model as an independent predictor of the development of dm . cox proportional hazards models for the prediction of dm or ms based on pfts * the model was reduced by stepwise selection . all covariates were candidates for removal . only those covariates that remained significant ( p  0.05 ) are shown in the table . the covariates considered in the model were age , sex , abdominal obesity , hypertension , per pack - year smoking , physical activity index , education level , and shs center . only those covariates that remained significant ( p  0.05 ) are shown in the table . similar analyses of data from participants who developed ms indicated that fev1-to - fvc ratio predicted dm ; however , neither fvc nor fev1 alone predicted this syndrome . as before , abdominal obesity was retained in the final model as an independent predictor for ms ( table 4 ) . further investigation of obesity showed a significant reduction in pulmonary function in obese participants measured either by wc or by bmi ( table 5 ) . compared with normal participants , ms and dm adults with obesity had greater reductions in their pft ( fvc , fev1 , fvc % predicted , and fev1 % predicted all ptrend < 0.05 ) . adjusted spirometry results for normal , ms , and dm groups by obesity status data are means ( 95% ci ) adjusted for age , sex , height , hypertension , physical activity index , education level , current smoking status , and shs center . ao , abdominal obesity ; obs , obesity . * ao was defined as wc > 102 cm in men and > 88 cm in women . in this study , adult ais with ms or dm had significantly lower fvc , fev1 , fvc % predicted , and fev1 % predicted compared with normal ai participants . this relationship persisted after adjustment for multiple factors , including obesity , and was related to metabolic disorders and markers of inflammation . major strengths of the current study are the inclusion of multiple measures of metabolic disorders and the consistency of the results for all these measurements . our results are also consistent with those of other studies ( 79 ) that show restrictive lung function ( reduced fvc and increased fev1-to - fvc ratio ) , but not obstructive pulmonary function ( decreased fev1-to - fvc ratio ) , to be associated with ms and dm . participants with ms had significantly lower fvc , fev1 , fvc % predicted , and fev1 % predicted compared with participants without dm or ms . our results are consistent with cross - sectional studies ( 7,8,18 ) . in patients with dm , the relationships were graded by dm severity and serum markers of inflammation after the adjustment for possible confounders . our results support cross - sectional studies , which demonstrate lower fvc and fev1 in adults with dm compared with their nondiabetic counterparts ( 1,19,20 ) , especially when dm was of longer duration and subjects required medication treatment ( 1 ) , had a higher homa score ( 19 ) and had higher levels of serum inflammatory markers ( 21 ) . previous studies suggest that impaired lung function predicts the subsequent development of clinical dm ( 5,6 ) ; studies also show that wc predicts dm beyond commonly evaluated cardiometabolic risk factors ( 22,23 ) . yet few studies have assessed whether the relationship between lung function and dm is mediated by central obesity . ( 18 ) found that the relationship between lung function impairment and ms was predominantly due to abdominal obesity ; our data also suggest that abdominal obesity is a significant factor that affects ms , dm , and pft . the underlying mechanisms relating this type of metabolic disorder to reduced lung function remain unclear ; integration of inflammatory and metabolic pathways in ms or dm patients may be an important underlying mechanism relating the disorders to reduced lung function ( 24 ) . in the current study , there was a significant , graded , and inverse relationship between pft and wc and/or bmi , indicating that obesity played a significant role in the relationship of reduced pft and metabolic disorders . there was also a significant , graded , and inverse relationship between lung function and inflammatory markers , indicating that inflammation played a significant role in the relationship of reduced pft and metabolic disorders . the strengths of this study include the community - based sample , standardized spirometric techniques , extensive data on potential confounders , and a large sample size that increased precision and permitted multiple statistical adjustments . the study s limitations include lack of generalizability of results to heavy / prolonged smokers and the lack of data on obesity - related inflammatory markers , which precluded more detailed investigations of the causal pathway . the main conclusions from the cross - sectional analyses are that reduced lung function is independently associated with ms and dm and that obesity and inflammation are associated with reduced lung function in ms and dm ; impaired lung function presents before the development of ms or dm in ais . further studies are needed to investigate how inflammation and obesity affect lung function in patients with ms and dm . in this study , adult ais with ms or dm had significantly lower fvc , fev1 , fvc % predicted , and fev1 % predicted compared with normal ai participants . this relationship persisted after adjustment for multiple factors , including obesity , and was related to metabolic disorders and markers of inflammation . major strengths of the current study are the inclusion of multiple measures of metabolic disorders and the consistency of the results for all these measurements . our results are also consistent with those of other studies ( 79 ) that show restrictive lung function ( reduced fvc and increased fev1-to - fvc ratio ) , but not obstructive pulmonary function ( decreased fev1-to - fvc ratio ) , to be associated with ms and dm . participants with ms had significantly lower fvc , fev1 , fvc % predicted , and fev1 % predicted compared with participants without dm or ms . our results are consistent with cross - sectional studies ( 7,8,18 ) . in patients with dm , the relationships were graded by dm severity and serum markers of inflammation after the adjustment for possible confounders . our results support cross - sectional studies , which demonstrate lower fvc and fev1 in adults with dm compared with their nondiabetic counterparts ( 1,19,20 ) , especially when dm was of longer duration and subjects required medication treatment ( 1 ) , had a higher homa score ( 19 ) and had higher levels of serum inflammatory markers ( 21 ) . previous studies suggest that impaired lung function predicts the subsequent development of clinical dm ( 5,6 ) ; studies also show that wc predicts dm beyond commonly evaluated cardiometabolic risk factors ( 22,23 ) . yet few studies have assessed whether the relationship between lung function and dm is mediated by central obesity . ( 18 ) found that the relationship between lung function impairment and ms was predominantly due to abdominal obesity ; our data also suggest that abdominal obesity is a significant factor that affects ms , dm , and pft . the underlying mechanisms relating this type of metabolic disorder to reduced lung function remain unclear ; integration of inflammatory and metabolic pathways in ms or dm patients may be an important underlying mechanism relating the disorders to reduced lung function ( 24 ) . in the current study , there was a significant , graded , and inverse relationship between pft and wc and/or bmi , indicating that obesity played a significant role in the relationship of reduced pft and metabolic disorders . there was also a significant , graded , and inverse relationship between lung function and inflammatory markers , indicating that inflammation played a significant role in the relationship of reduced pft and metabolic disorders . the strengths of this study include the community - based sample , standardized spirometric techniques , extensive data on potential confounders , and a large sample size that increased precision and permitted multiple statistical adjustments . the study s limitations include lack of generalizability of results to heavy / prolonged smokers and the lack of data on obesity - related inflammatory markers , which precluded more detailed investigations of the causal pathway . the main conclusions from the cross - sectional analyses are that reduced lung function is independently associated with ms and dm and that obesity and inflammation are associated with reduced lung function in ms and dm ; impaired lung function presents before the development of ms or dm in ais . further studies are needed to investigate how inflammation and obesity affect lung function in patients with ms and dm .
objectivethe purposes of this study were to investigate whether reduced lung function is associated with metabolic syndrome ( ms ) and diabetes ( dm ) in american indians ( ais ) and to determine whether lower pulmonary function presents before the development of dm or ms.research design and methodsthe strong heart study ( shs ) is a multicenter , prospective study of cardiovascular disease ( cvd ) and its risk factors among ai adults . 
 the present analysis used lung function assessment by standard spirometry at the shs second examination ( 19931995 ) in 2,396 adults free of overt lung disease or cvd , with or without dm or ms . among ms - free / dm - free participants , 
 the development of ms / dm at the shs third examination ( 19961999 ) was investigated.resultssignificantly lower pulmonary function was observed for ais with ms or dm . 
 impaired pulmonary function was associated with ms and dm after adjustment for age , sex , abdominal obesity , current smoking status , physical activity index , hypertension , and shs field center . 
 both forced vital capacity ( fvc ) and forced expiratory volume in 1 s ( fev1 ) were negatively associated with insulin resistance or dm severity and with serum markers of inflammation ( p < 0.05 ) . 
 fvc and fev1-to - fvc ratio both predicted dm in unadjusted analyses but not when adjusted for covariates , including waist circumference . in the adjusted model , 
 abdominal obesity predicted both ms and dm.conclusionsreduced lung function is independently associated with ms and with dm , and impaired lung function presents before the development of ms or dm ; these associations may result from the effects of obesity and inflammation .