the nurses ' health study ii ( nhs ii ) is a prospective cohort study of 116,671 female u.s .
. this cohort has been , and continues to be , followed with the use of biennial mailed questionnaires to update information on health - related behavior and to determine incident disease outcome .
the follow - up rate has been 90% for every 2-year period . in the present analysis , women were excluded if they did not complete a semiquantitative food frequency questionnaire ( sffq ) in 1991 ; if more than 70 items on the sffq were left blank ; if their reported total energy intake was implausible ( < 500 kcal / day or > 3,500 kcal / day ) ; if they reported a multiple gestation ( twins or higher - order multiple gestation ) ; if they did not provide physical activity data in 1991 ; or if they reported a history of diabetes , cancer , cardiovascular disease , or gdm on the 1989 or 1991 questionnaires . the final sample for the current analyses consisted of 13,475 women who reported having at least one singleton pregnancy lasting 6 months or more between 1992 and 2001 .
gdm case subjects were identified based on self - reported information in the biennial questionnaire .
a previous validation study based on medical record review demonstrated a high validity of self - reported diagnosis of gdm in this cohort ( 10 ) . in brief ,
medical records were reviewed among a sample of 114 women in the cohort who corroborated on a supplementary questionnaire that they had a first diagnosis of gdm in a singleton pregnancy between 1989 and 1991 .
supplementary questionnaires were also sent to 100 women reporting a pregnancy uncomplicated by gdm during the same interval .
a singleton pregnancy during this period was confirmed for 93 responders . among them , 83% reported a glucose loading test and all ( 100% ) reported frequent urine screening in pregnancy , consistent with a high degree of surveillance in this cohort .
dietary intake information was collected by a 133-item sffq designed to assess average food intake over the previous year .
women were asked how often they had consumed a specified amount of each food on average over the previous year . for beverages , one serving ( considered as one glass , bottle , or can ) was used as the unit for the consumption of ssbs .
the original sffq included four items for ssbs including  coke , pepsi , or other cola with sugar ,   caffeine - free coke , pepsi , or other cola with sugar ,   other carbonated beverages with sugar ,  and  fruit punch ,  as well as three items for diet beverages including  low - calorie cola with caffeine , 
 low - calorie caffeine - free cola ,  and  other low - calorie beverages .
 in the primary analysis , we summed the intakes of single items for the above beverage categories to generate the total consumptions of ssbs and of diet beverages . in the secondary analysis
, we also created several subgroups under each major beverage category : two subgroups for the ssb category ( sugar - sweetened cola including  coke , pepsi , or other cola with sugar  and  caffeine - free coke , pepsi , or other cola with sugar  and other ssbs including  other carbonated beverages with sugar  and  fruit punch  ) and two subgroups for the diet beverages category ( diet cola including  low - calorie cola with caffeine  and  low - calorie caffeine - free cola  and other diet beverages including  other low - calorie beverages  ) .
nutrient intakes were computed by multiplying the frequency response by the nutrient content of the specified portion sizes and summing the contributions of all foods .
food composition values were obtained from the harvard university food composition database , which was derived from u.s .
the validity and reliability of sffqs similar to those used in the nhs ii were described elsewhere ( 11,12 ) . corrected correlation coefficients between the sffq and multiple dietary records were 0.84 for cola - type soft drinks ( sugar - sweetened and diet combined ) , 0.56 for other carbonated soft drinks , and 0.56 for fruit punch in a similar cohort of women ( the nhs ) ( 12 ) and were 0.84 for sugar - sweetened cola , 0.55 for other sugar - sweetened soft drinks , 0.73 for diet cola , and 0.74 for other diet soft drinks in the health professionals follow - up study ( 11 ) .
participants ' sociodemographic , clinical , and lifestyle information was collected at baseline and updated biennially .
bmi was calculated by self - reported weight and height ( weight in kilograms divided by the square of height in meters ) .
self - reports of body weight were highly correlated with technician - measured weight ( r = 0.96 ) in a similar cohort ( 10,13 ) .
participants were asked to report weekly activities for each of the following categories : walking or hiking outdoors ; jogging ; running ; bicycling ; lap swimming ; tennis , squash , or racquetball playing ; calisthenics ; and other recreation . from this information , weekly energy expenditure in met hours was calculated and used to represent total discretionary physical activity in the analyses .
family history of diabetes and other diseases was reported in 1989 . in the primary analyses , we created measures of cumulative average intakes of ssb to represent long - term intakes before gdm was diagnosed .
for instance , the 1991 intake was used for the follow - up between 1991 and 1995 , and the average of the 1991 and 1995 intake was used for the follow - up between 1995 and 1999 to reduce within - person variation .
ssb consumption was analyzed both as a categorical variable ( 03 servings / month , 14 servings / week , 5 servings / week ) and a continuous variable ( servings / day ) . because women with previous gdm were excluded from this study and women with a previous pregnancy uncomplicated by gdm are less likely than nulliparous women ( i.e. , women whose index pregnancy is their first termed pregnancy ) to develop gdm , nulliparous women were overrepresented in the gdm group . to account for this effect , we adjusted for parity in multivariate analyses and performed a secondary analysis by restricting our analysis to nulliparous women .
we performed multivariate cox proportional hazards analyses to estimate relative risks ( rrs ) and 95% cis while controlling for potential confounding factors .
subsequent models were built with inclusion of potential confounders , including race / ethnicity ( caucasian , african american , hispanic , and asian ) , family history of diabetes ( yes or no ) , smoking status ( never , past , or current ) , physical activity ( quintiles ) , and alcohol consumption ( 0 , 0.1 4.9 , 5.09.9 , and > 10 g / day ) . because bmi might represent intermediate variables in the relationship between beverage consumption and gdm risk , we adjusted for bmi ( < 21 , 2122.9 , 23.024.9 , 25.026.9 , 27.028.9 , 29.030.9 , 31.032.9 , 33.034.9 , and > 35.0
in addition , we constructed dietary pattern scores using key food items that characterized the western and prudent dietary patterns as described previously ( 14 ) .
the western dietary pattern included red meat , processed meat , refined grain products , snacks , sweets and desserts ( not including ssbs ) , french fries , and pizza ; the prudent dietary pattern included fruits , tomatoes , cabbages , green leafy vegetables , dark - yellow vegetables , legumes , other vegetables , poultry , and fish ( 14 ) .
these simplified dietary pattern variables were highly correlated ( r > 0.92 ) with the patterns derived from the factor analysis in our study population ( 15 ) .
the significance of the linear trends across categories of beverage intake was evaluated using the median value for each category of beverage intake and analyzed as a continuous variable in multivariate models .
we evaluated whether associations between consumption of ssbs and the risk of gdm were modified by bmi ( < 25 or 5 kg / m ) , nulliparity ( yes or no ) , smoking habit ( never , past , or current smoker ) , or family history of diabetes ( yes or no ) using stratified analyses and by evaluating interaction terms .
all statistical analyses were performed by using sas statistical software ( version 8.2 ; sas institute , cary , nc ) .
gdm case subjects were identified based on self - reported information in the biennial questionnaire .
a previous validation study based on medical record review demonstrated a high validity of self - reported diagnosis of gdm in this cohort ( 10 ) . in brief ,
medical records were reviewed among a sample of 114 women in the cohort who corroborated on a supplementary questionnaire that they had a first diagnosis of gdm in a singleton pregnancy between 1989 and 1991 .
supplementary questionnaires were also sent to 100 women reporting a pregnancy uncomplicated by gdm during the same interval .
a singleton pregnancy during this period was confirmed for 93 responders . among them , 83% reported a glucose loading test and all ( 100% ) reported frequent urine screening in pregnancy , consistent with a high degree of surveillance in this cohort .
dietary intake information was collected by a 133-item sffq designed to assess average food intake over the previous year .
women were asked how often they had consumed a specified amount of each food on average over the previous year . for beverages , one serving ( considered as one glass , bottle , or can ) was used as the unit for the consumption of ssbs .
the original sffq included four items for ssbs including  coke , pepsi , or other cola with sugar , 
 caffeine - free coke , pepsi , or other cola with sugar ,   other carbonated beverages with sugar ,  and  fruit punch ,  as well as three items for diet beverages including  low - calorie cola with caffeine , 
 low - calorie caffeine - free cola ,  and  other low - calorie beverages .  in the primary analysis , we summed the intakes of single items for the above beverage categories to generate the total consumptions of ssbs and of diet beverages . in the secondary analysis
, we also created several subgroups under each major beverage category : two subgroups for the ssb category ( sugar - sweetened cola including  coke , pepsi , or other cola with sugar  and  caffeine - free coke , pepsi , or other cola with sugar  and other ssbs including  other carbonated beverages with sugar  and  fruit punch  ) and two subgroups for the diet beverages category ( diet cola including  low - calorie cola with caffeine  and  low - calorie caffeine - free cola  and other diet beverages including  other low - calorie beverages  ) .
nutrient intakes were computed by multiplying the frequency response by the nutrient content of the specified portion sizes and summing the contributions of all foods .
food composition values were obtained from the harvard university food composition database , which was derived from u.s .
the validity and reliability of sffqs similar to those used in the nhs ii were described elsewhere ( 11,12 ) . corrected correlation coefficients between the sffq and multiple dietary records were 0.84 for cola - type soft drinks ( sugar - sweetened and diet combined ) , 0.56 for other carbonated soft drinks , and 0.56 for fruit punch in a similar cohort of women ( the nhs ) ( 12 ) and were 0.84 for sugar - sweetened cola , 0.55 for other sugar - sweetened soft drinks , 0.73 for diet cola , and 0.74 for other diet soft drinks in the health professionals follow - up study ( 11 ) .
participants ' sociodemographic , clinical , and lifestyle information was collected at baseline and updated biennially .
bmi was calculated by self - reported weight and height ( weight in kilograms divided by the square of height in meters ) .
self - reports of body weight were highly correlated with technician - measured weight ( r = 0.96 ) in a similar cohort ( 10,13 ) .
participants were asked to report weekly activities for each of the following categories : walking or hiking outdoors ; jogging ; running ; bicycling ; lap swimming ; tennis , squash , or racquetball playing ; calisthenics ; and other recreation . from this information , weekly energy expenditure in met hours was calculated and used to represent total discretionary physical activity in the analyses .
in the primary analyses , we created measures of cumulative average intakes of ssb to represent long - term intakes before gdm was diagnosed .
for instance , the 1991 intake was used for the follow - up between 1991 and 1995 , and the average of the 1991 and 1995 intake was used for the follow - up between 1995 and 1999 to reduce within - person variation .
ssb consumption was analyzed both as a categorical variable ( 03 servings / month , 14 servings / week , 5 servings / week ) and a continuous variable ( servings / day ) . because women with previous gdm were excluded from this study and women with a previous pregnancy uncomplicated by gdm are less likely than nulliparous women ( i.e. , women whose index pregnancy is their first termed pregnancy ) to develop gdm , nulliparous women were overrepresented in the gdm group . to account for this effect , we adjusted for parity in multivariate analyses and performed a secondary analysis by restricting our analysis to nulliparous women .
we performed multivariate cox proportional hazards analyses to estimate relative risks ( rrs ) and 95% cis while controlling for potential confounding factors .
subsequent models were built with inclusion of potential confounders , including race / ethnicity ( caucasian , african american , hispanic , and asian ) , family history of diabetes ( yes or no ) , smoking status ( never , past , or current ) , physical activity ( quintiles ) , and alcohol consumption ( 0 , 0.1 4.9 , 5.09.9 , and > 10 g / day ) . because bmi might represent intermediate variables in the relationship between beverage consumption and gdm risk , we adjusted for bmi ( < 21 , 2122.9 , 23.024.9 , 25.026.9 , 27.028.9 , 29.030.9 , 31.032.9 , 33.034.9 , and > 35.0
in addition , we constructed dietary pattern scores using key food items that characterized the western and prudent dietary patterns as described previously ( 14 ) .
the western dietary pattern included red meat , processed meat , refined grain products , snacks , sweets and desserts ( not including ssbs ) , french fries , and pizza ; the prudent dietary pattern included fruits , tomatoes , cabbages , green leafy vegetables , dark - yellow vegetables , legumes , other vegetables , poultry , and fish ( 14 ) .
these simplified dietary pattern variables were highly correlated ( r > 0.92 ) with the patterns derived from the factor analysis in our study population ( 15 ) .
the significance of the linear trends across categories of beverage intake was evaluated using the median value for each category of beverage intake and analyzed as a continuous variable in multivariate models .
we evaluated whether associations between consumption of ssbs and the risk of gdm were modified by bmi ( < 25 or 5 kg / m ) , nulliparity ( yes or no ) , smoking habit ( never , past , or current smoker ) , or family history of diabetes ( yes or no ) using stratified analyses and by evaluating interaction terms .
all statistical analyses were performed by using sas statistical software ( version 8.2 ; sas institute , cary , nc ) .
during 10 years of follow - up , 860 women reported their first diagnosis of gdm among the 13,475 women included in this study . on average , women in this population consumed fewer ssbs than diet beverages . at baseline ,
the median intake was 1 serving / week for ssbs and 24 servings / week for diet beverages .
the percentages of women who reported consuming ssbs of 03 servings / month , 24 servings / week , and 5 servings / week were 41.4 , 27.3 , and 33.3% , respectively . by volume ,
34% of ssbs consumed was from sugar - sweetened cola and 66% was from other ssbs . for diet beverages ,
the percentages of women who reported consuming 03 servings / month , 24 servings / week , and 5 servings / week were 38.3 , 15.3 , and 46.4% , respectively
. of diet beverages consumed , 81% was from diet cola and 19% was from other diet beverages .
women with a higher intake of ssbs were on average younger and less likely to have a family history of diabetes or drink alcohol ( table 1 ) .
these women tended to consume a diet higher in total calories , total carbohydrates , processed and red meats , and glycemic load but lower in protein , fat , total dietary fiber , fruits and vegetables , and selected minerals and vitamins ( magnesium , calcium , potassium , and vitamins c and e ) .
baseline ( 1991 ) characteristics according to the frequencies of ssb consumption in 13,475 women data are
means  se , unless otherwise indicated . after adjusting for age and parity ( table 2 ; model 1 )
, higher ssb intake was positively associated with gdm risk : compared with women who consumed < 1 serving / month ( reference group ) , rr for those who consumed 5 servings / week was 1.23 ( 95% ci 1.051.45 ; ptrend = 0.005 ) .
the positive association between ssbs and gdm risk remained significant after adjustment for other demographic and lifestyle risk factors for gdm , including race , smoking , alcohol intake , physical activity , and family history of diabetes , in model 2 ( ptrend = 0.04 ) .
this association remained strong after additional adjustment for bmi ( model 3 ) . when ssb intake was treated as a continuous variable in model 3 ,
each serving / day increment was associated with a 23% ( 95% ci 1.051.43 ; ptrend = 0.01 ) increase in gdm risk .
the association was slightly attenuated and became borderline insignificant ( p = 0.06 ) with additional adjustment of western dietary pattern ( model 4 ) . however , the trend for an elevated risk of gdm associated with increased ssb consumption persisted : the rrs ( 95% cis ) from the lowest to the highest ssb consumption category in model 4 were 1.00 ( reference ) , 1.03 ( 0.871.23 ) , and 1.16 ( 0.981.37 ) .
further controlling for prudent dietary pattern and other beverage consumption including diet beverages and fruit juices did not change the results materially .
rr of gdm in relation to ssb consumption ( n = 13,475 ; case subjects = 860 ) data are rr ( 95% ci ) unless otherwise indicated . * model 1 adjusted for age ( 5-year category ) and parity ( 0 , 1 , 2 , or 3 ) .
model 2 adjusted for variables in model 1 plus race / ethnicity , cigarette smoking status ( never , past , or current ) , family history of diabetes in a first - degree relative ( yes or no ) , alcohol intake ( 5 categories : 0 , 0.15.0 , 5.115.0 , or > 15 g / day ) , and physical activity ( quintile ) . model 3 adjusted for variables in model 2 plus bmi ( 9 categories : < 21.0 , 21.022.9 , 23.024.9 , 25.026.9 , 27.028.9 , 29.030.9 , 31.032.9 , 33.034.9 , or 35.0 kg / m ) .
 model 4 adjusted for variables in model 3 plus western dietary pattern score ( quintile ) . in the stratified analysis according to participants ' bmi status ( < 25 or 25 kg / m ) , family history of diabetes ( yes or no ) , smoking habit ( never , past , or current smoking ) , or nulliparity ( yes or no ) , the direction of the association between gdm risk and ssb consumption was consistent in each strata .
the magnitude of the association , however , appeared to be stronger among nulliparous women ( pinteraction = 0.004 ) .
because caramel coloring in cola - type beverages has been positively associated with insulin resistance and inflammation in animals ( 16 ) , we further examined the associations between two types of ssbs ( cola versus noncola ) and gdm risk .
a positive association with gdm risk was found for sugar - sweetened cola but not for noncola ssbs ( table 2 ) . compared with women who consumed sugar - sweetened cola of 03 servings / month ,
those who consumed 5 servings / week had a 22% increase in gdm risk ( rr 1.22 [ 95% ci 1.011.47 ] ; ptrend = 0.04 ) after controlling for other potential confounders ( model 4 ) .
we also assessed whether consumption of diet beverages was associated with gdm risk . for total diet beverages
, the results did not show any association in all models , regardless of whether consumption was treated as a categorical variable or a continuous variable ( table 3 ) .
we further examined the relationship between two types of diet beverages ( diet cola or other diet beverages ) and risk of gdm .
however , this positive association disappeared after additional adjustment for bmi and other dietary variables in models 3 and 4 .
rr of gdm in relation to diet beverage consumption ( n = 13,475 , cases = 860 ) data are rr ( 95% ci ) unless otherwise indicated .
* model 1 adjusted for age ( 5-year category ) and parity ( 0 , 1 , 2 , or 3 ) .
model 2 adjusted for variables in model 1 plus race / ethnicity , cigarette smoking status ( never , past , or current ) , family history of diabetes in a first - degree relative ( yes or no ) , alcohol intake ( 5 categories : 0 , 0.15.0 , 5.115.0 , or >
model 3 adjusted for variables in model 2 plus bmi ( 9 categories : < 21.0 , 21.022.9 , 23.024.9 , 25.026.9 , 27.028.9 , 29.030.9 , 31.032.9 , 33.034.9 , or 35.0 kg / m . )
 model 4 adjusted for variables in model 3 plus western dietary pattern score ( quintile ) and ssbs .
in this large prospective study , we observed that pregravid consumption of sugar - sweetened cola was significantly and positively associated with gdm risk , after adjustment of known risk factors for gdm including age , family history of diabetes , parity , physical activity , smoking status , alcohol intake bmi , and western dietary pattern .
compared with women who consumed < 1 serving / month , those who consumed 5 servings / week of sugar - sweetened cola had a 22% greater gdm risk . no statistically significant elevation in risk
although the underlying mechanism remains unclear , available evidence suggests that the main defect in the pathogenesis of gdm is relatively diminished insulin secretion coupled with pregnancy - induced insulin resistance ( 17 ) .
thus , pregnancy - related metabolic challenges unmask a predisposition to glucose metabolic disorders in some women .
factors that contribute to insulin resistance or impaired insulin secretion before pregnancy and in early pregnancy can have a deleterious effect during pregnancy and be risk factors for gdm .
several possible explanations may help to understand the positive association between sugar - sweetened cola consumption and gdm risk .
first , consuming a large amount of sugar - sweetened cola could contribute to a high  glycemic load ( gl ) diet by providing a large amount of rapidly absorbable sugars .
high - gl foods or diets were observed to induce a greater postprandial plasma glucose response . although results from human metabolic studies on the impact of gl on insulin sensitivity and secretion are still inconclusive , findings from well - designed studies tend to suggest that a lower - gl diet may improve insulin sensitivity in both normal individuals and patients with impaired glucose intolerance . in crossover studies where insulin sensitivity was measured by euglycemic - hyperinsulinemic
clamp , a low - gl diet was found to lead to higher whole - body glucose uptake than the high - gl diet in men with type 2 diabetes ( 18 ) . in a recent meta - analysis on intervention studies ,
a 20% improvement in insulin sensitivity was estimated from 18 studies in healthy individuals as well as diabetic or obese individuals ( 19 ) .
in addition , higher - gl diet has been related to an elevated gdm risk in the nhs ii population ( 20 ) .
a recent study found that higher sugar intake ( 50% of sugar derived from ssbs ) was inversely associated with insulin secretion ( measured by acute insulin response ) and -cell function ( measured by disposition index ) after adjusting for body composition and other confounders among children ( 5 ) .
it has been proposed that consumption of foods high in sugar could lead to the accumulation of reactive oxygen species in -cells that will subsequently cause -cell damage and dysfunction ( 21 ) .
third , caramel coloring in cola - type soft drinks is rich in advanced glycation end products ( ages ) .
emerging evidence suggests that ages may be positively associated with insulin resistance and inflammation ( 16 ) . that may help to explain why a stronger association was observed for consumption of sugar - sweetened cola than other ssbs
however , we did not find associations between diet cola and gdm risk , suggesting that ages alone may not be a major contributor to the observed association between sugar - sweetened cola consumption and risk of gdm . due to the observational nature of the present study
further studies to explore whether ages and sugars together could have a synergistic effect on insulin resistance or -cell damage are needed .
our study has several strengths including the prospective design , large sample size , and repeated measurements of exposure variables and covariates .
first , the sffq , similar to those used in the nhs ii cohort , has been validated against multiple weeks of food records completed over the previous year and showed good correlations ( 11,12 ) .
although misclassification of dietary ssb intake is inevitable , these dietary data could not have been influenced by the subsequent development of gdm because of the prospective design of this study .
this would be expected to attenuate the observed associations , which would not explain the positive results .
second , because of the observational nature of our study , we can not prove the causality of the observed association and rule out the impact of residual confounding , although we controlled for most known risk factors of gdm . however
, this population is relatively homogeneous regarding socioeconomic status and occupational environments , which tended to reduce the impact of unknown or unmeasured confounders .
women might change their diets after knowing they are pregnant and receiving dietary counseling or due to the change of their appetite ( 22,23 ) .
it is possible that such changes may have an acute effect on gdm risk or may modify the effects of pre - gravid beverage consumption on gdm risk .
however , there is evidence suggesting that such a pregnancy - related change in dietary intake is item specific and is not substantially for ssbs .
for instance , in a prospective study among 2,128 pregnant women ( 24 ) , ssb consumption did not change appreciably from the last menstrual period before pregnancy to 2628 weeks of pregnancy .
lastly , participants in the nhs ii cohort do not represent a random sample of u.s .
women : the majority of our study participants are health professionals and tend to have a slightly healthier diet and lifestyle than the general u.s . population .
nonetheless , even among this population with low ssb intakes ( mean 0.52 vs. 2.18 servings / day in national representative samples ) ( 25 ) , we observed significantly elevated risk of gdm associated with the consumption of sugar - sweetened cola
in summary , findings from this large prospective study suggest that higher consumption of sugar - sweetened cola ( 5 servings / week ) is significantly associated with an elevated risk of gdm .
further studies in other populations regarding the relation between the consumption of ssbs and risk of gdm as well as other pregnancy - related outcomes are warranted .
 objectiveconsumption of sugar - sweetened beverages ( ssbs ) was related to an elevated risk of type 2 diabetes and insulin resistance in several recent studies among middle- or older - aged populations . 
 studies on ssb consumption and glucose intolerance among pregnant women , however , are lacking . 
 we therefore examined the association between regular ssb consumption before pregnancy and the risk of gestational diabetes mellitus ( gdm).research design and methodsthis was a prospective study among 13,475 u.s . 
 women who reported at least one singleton pregnancy between 1992 and 2001 in the nurses ' health study ii . 
 gdm was self - reported and validated by medical record review in a subsample . 
 cox proportional hazards models with multivariate adjustments were applied to examine the association of ssb consumption with gdm risk.resultsduring 10 years of follow - up , 860 incident gdm case subjects were identified . 
 after adjustment for age , parity , race , physical activity , smoking , alcohol intake , prepregnancy bmi , and western dietary pattern , intake of sugar - sweetened cola was positively associated with the risk of gdm , whereas no significant association was found for other ssbs and diet beverages . compared with women who consumed < 1 serving / month , those who consumed 5 servings / week of sugar - sweetened cola had a 22% greater gdm risk ( relative risk 1.22 [ 95% ci 1.011.47]).conclusionsfindings from this study suggest that prepregnancy higher consumption of sugar - sweetened cola ( 5 servings / week ) is associated with an elevated gdm risk , whereas no significant association with gdm risk was observed for other ssbs and diet beverages . 
RESEARCH DESIGN AND METHODS
Ascertainment of GDM
Dietary assessment
Assessment of nondietary covariates
Statistical analysis
RESULTS
CONCLUSIONS