currently , basalbolus insulin therapy is used to provide the insulin secretory patterns most physiologically similar to normal . basalbolus therapy includes multiple daily injection ( mdi ) and continuous subcutaneous insulin infusion ( csii ) therapies . the recent advent of rapidacting insulin analogs and longacting insulin analogs , and the development of csii therapy using rapidacting insulin have clarified the role of basal and bolus insulin . few studies , however , have focused on factors associated with basal insulin doses . although basal insulin doses for japanese patients with type 1 diabetes mellitus were reported to be lower than those of type 1 diabetes mellitus patients in europe and the us , the reasons for this have not been clarified . japanese meals are known to have a higher carbohydrate energy ratio of meal ( cer ) and a lower fat energy ratio of meal ( fer ) than western meals . according to the statistics of the united nations , based on the amounts supplied , the fer in japan is 28% while those in western countries exceed 35% or even 40% . we speculated that differences in meal contents might be responsible for the differing basal insulin doses . to investigate determinants of basal insulin doses for basalbolus therapy in japanese patients with type 1 diabetes mellitus , we examined associations of potential factors , including age , sdsbmi ( standard deviation score of body mass index ) , hba1c levels and meal contents based on meal records , with basal insulin doses . fortyone outpatients with type 1 diabetes mellitus between the ages of 3 and 26 ( 20 males and 21 females , means age 15.9 ) were enrolled . patients with a duration of diabetes of < 2  years , hba1c levels of 9.0% or more , diabetic complications , or who were pregnant and/or had other diseases were excluded . the following variables were examined : gender , age , height , weight , sdsbmi , hba1c level , duration of diabetes , insulin administration method ( mdi or csii ) , daily bolus insulin doses ( bod ) , daily basal insulin doses ( bad ) , total daily insulin doses ( tdd ) , bad / tdd ( bt ratio ) , the value obtained by dividing bad by bw ( bad / bw ) and meal contents . in order to calculate the sdsbmi for the 12 patients aged 19 or over ( for which there is no recorded data in japan ) , each age used the data of 18.5  years old . the value for hba1c ( % ) is estimated as a national glycohemoglobin standardization program ( ngsp ) equivalent value ( % ) calculated by the formula hba1c ( % )  =  hba1c ( jds : japan diabetes society ) ( % )  +  0.4% , considering the relational expression of hba1c ( jds ) ( % ) measured by the previous japanese standard substance and measurement methods and hba1c ( ngsp ) . insulin doses for mdi therapy were obtained from the patients themselves or from medical records . insulin doses for csii therapy were obtained by reading the records on the pump used via the comstation ( mmt7301u ) ( medtronic diabetes , northridge , ca , usa ) . the doses of daily bolus insulin and daily basal insulin were checked every day for 3  days when the patients took pictures of their meals as described in detail below and the average values of three data were used for analysis . all subjects were treated with either mdi or csii employing basalbolus therapy . as to rapidacting insulin analogs , either lispro or aspart was used . patients given csii were received a bolus of normal type for bolus insulin dosing , during the study period . patients were instructed to adjust the basal insulin dose to keep blood glucose levels stable while they were not eating or not receiving the additional insulin . instructions of carbohydrate counting were provided at outpatient visits by a physician or by a dietitian working in our hospital . the photographs were taken with a digital camera or a mobile phone equipped with a camera . the meals included all breakfasts , lunches , dinners , and snacks , as well as supplemental food consumed at the time of hypoglycemia attacks . when the photographs were taken , something ( e.g. , a coin ) was placed beside the food to provide a size marker for length assessment . the dietitians estimated all ingredients and their weights from the photographs and calculated the ingested amounts ( in grams ) of protein , fat , and carbohydrate . they entered data for each ingredient using the computer software program excel eiyokun , version 4.0 ( kenpaku co. ltd . , excel eiyokun is a program designed to calculate amounts of protein , fat , and carbohydrate by entering the name and weight of a meal ingredient . the mean ingested amount of each nutrient ( daily protein , fat , and carbohydrate intakes ) as determined by the three dietitians was used for the analysis . the protein energy ratio of meal ( per ) was calculated by the following equation : daily protein intake ( g )    4/daily total energy ( kcal ) . the fat energy ratio of meal ( fer ) was calculated by the following equation : daily fat intake ( g )    9/daily total energy ( kcal ) . the carbohydrate energy ratio of meal ( cer ) was calculated by the following equation : daily carbohydrate intake ( g )    4/daily total energy ( kcal ) . the ethics committee of osaka city university institutional review board , osaka , japan , approved this protocol . intergroup comparisons were performed for age , sdsbmi , hba1c levels , duration of diabetes , bt ratio , bad / bw and meal contents , according to gender and therapy ( mdi or csii ) , using the ttest or the mann subsequently , to evaluate simple correlations with basal insulin doses , associations of the bt ratio or bad / bw with age , sdsbmi , hba1c levels , duration of diabetes and each meal content variable were examined using pearson s productmoment correlations . next , multiple regression analysis was performed for all subjects and for each age group to evaluate factors influencing bad without interactions among the variables examined . the dependent variable selected was bad / bw . the independent variables selected were : gender ( female  =  0 , male  =  1 ) , age , sdsbmi , hba1c levels , therapy ( mdi  =  0 , csii  =  1 ) , and fat energy ratio . for the analysis of age effect , patients were divided into four age groups . patients aged 9 or younger were age group 1 , patients between the age of 10 and 13 were age group 2 , patients between the age of 14 and 18 were age group 3 , and patients aged 19 or above were age group 4 . then patients were divided by sex ( male and female group ) and hba1c levels ( good < 7% and poorly controlled > 7% group ) . differences with p  <  0.05 were considered to be statistically significant . for multiple regression analysis , the stepwise method was used with the following criteria : probability of entering f : 0.050 and probability of removing f : 0.100 . fortyone outpatients with type 1 diabetes mellitus between the ages of 3 and 26 ( 20 males and 21 females , means age 15.9 ) were enrolled . patients with a duration of diabetes of < 2  years , hba1c levels of 9.0% or more , diabetic complications , or who were pregnant and/or had other diseases were excluded . the following variables were examined : gender , age , height , weight , sdsbmi , hba1c level , duration of diabetes , insulin administration method ( mdi or csii ) , daily bolus insulin doses ( bod ) , daily basal insulin doses ( bad ) , total daily insulin doses ( tdd ) , bad / tdd ( bt ratio ) , the value obtained by dividing bad by bw ( bad / bw ) and meal contents . in order to calculate the sdsbmi for the 12 patients aged 19 or over ( for which there is no recorded data in japan ) , each age used the data of 18.5  years old . the value for hba1c ( % ) is estimated as a national glycohemoglobin standardization program ( ngsp ) equivalent value ( % ) calculated by the formula hba1c ( % )  =  hba1c ( jds : japan diabetes society ) ( % )  +  0.4% , considering the relational expression of hba1c ( jds ) ( % ) measured by the previous japanese standard substance and measurement methods and hba1c ( ngsp ) . insulin doses for mdi therapy were obtained from the patients themselves or from medical records . insulin doses for csii therapy were obtained by reading the records on the pump used via the comstation ( mmt7301u ) ( medtronic diabetes , northridge , ca , usa ) . the doses of daily bolus insulin and daily basal insulin were checked every day for 3  days when the patients took pictures of their meals as described in detail below and the average values of three data were used for analysis . all subjects were treated with either mdi or csii employing basalbolus therapy . as to rapidacting insulin analogs , either lispro or aspart was used . patients given csii were received a bolus of normal type for bolus insulin dosing , during the study period . patients were instructed to adjust the basal insulin dose to keep blood glucose levels stable while they were not eating or not receiving the additional insulin . instructions of carbohydrate counting were provided at outpatient visits by a physician or by a dietitian working in our hospital . the photographs were taken with a digital camera or a mobile phone equipped with a camera . the meals included all breakfasts , lunches , dinners , and snacks , as well as supplemental food consumed at the time of hypoglycemia attacks . when the photographs were taken , something ( e.g. , a coin ) was placed beside the food to provide a size marker for length assessment . the dietitians estimated all ingredients and their weights from the photographs and calculated the ingested amounts ( in grams ) of protein , fat , and carbohydrate . they entered data for each ingredient using the computer software program excel eiyokun , version 4.0 ( kenpaku co. ltd . , excel eiyokun is a program designed to calculate amounts of protein , fat , and carbohydrate by entering the name and weight of a meal ingredient . the mean ingested amount of each nutrient ( daily protein , fat , and carbohydrate intakes ) as determined by the three dietitians was used for the analysis . the protein energy ratio of meal ( per ) was calculated by the following equation : daily protein intake ( g )    4/daily total energy ( kcal ) . the fat energy ratio of meal ( fer ) was calculated by the following equation : daily fat intake ( g )    9/daily total energy ( kcal ) . the carbohydrate energy ratio of meal ( cer ) was calculated by the following equation : daily carbohydrate intake ( g )    4/daily total energy ( kcal ) . the ethics committee of osaka city university institutional review board , osaka , japan , approved this protocol . intergroup comparisons were performed for age , sdsbmi , hba1c levels , duration of diabetes , bt ratio , bad / bw and meal contents , according to gender and therapy ( mdi or csii ) , using the ttest or the mann subsequently , to evaluate simple correlations with basal insulin doses , associations of the bt ratio or bad / bw with age , sdsbmi , hba1c levels , duration of diabetes and each meal content variable were examined using pearson s productmoment correlations . next , multiple regression analysis was performed for all subjects and for each age group to evaluate factors influencing bad without interactions among the variables examined . the dependent variable selected was bad / bw . the independent variables selected were : gender ( female  =  0 , male  =  1 ) , age , sdsbmi , hba1c levels , therapy ( mdi  =  0 , csii  =  1 ) , and fat energy ratio . for the analysis of age effect , patients were divided into four age groups . patients aged 9 or younger were age group 1 , patients between the age of 10 and 13 were age group 2 , patients between the age of 14 and 18 were age group 3 , and patients aged 19 or above were age group 4 . then patients were divided by sex ( male and female group ) and hba1c levels ( good < 7% and poorly controlled > 7% group ) . differences with p  <  0.05 were considered to be statistically significant . for multiple regression analysis , the stepwise method was used with the following criteria : probability of entering f : 0.050 and probability of removing f : 0.100 . the averages of key characteristics were as follows : age , 15.9    5.4  years ; sdsbmi , 0.86    0.83 ; duration of diabetes , 9.8    5.7  years ; hba1c levels 7.2    0.7% ; bt ratio , 0.35    0.09 ( mdi : 0.33 , csii : 0.37 ) ; and bad / bw , 0.35    0.12  u / kg ( mdi : 0.36 csii : 0.34  u / kg ) . the average of differences for 3  days in fer was 6    3% . tdd , total daily insulin doses ; bt ratio , daily basal insulin doses / total daily insulin doses ; bad / bw , daily basal insulin doses / body weight ; tdd / bw , total daily insulin doses / body weight ; per , protein energy ratio of meal ; fer , fat energy ratio of meal ; cer , carbohydrate energy ratio of meal ; energy , total energy intake . based on the assessments made by the three experienced dietitians , the mean per was 0.16 , the mean fer was 0.30 , and the mean cer was 0.52 in 41 patients . the total daily grams of protein , fat , and carbohydrate were 107 , 76 , and 359  g , respectively . protein energy , fat energy , and carbohydrate energy ratios were 0.16 , 0.26 , and 0.55 , respectively . in intergroup comparisons , regardless of gender or insulin administration method ( mdi or csii ) , there were no intergroup statistical differences in sdsbmi , bad / bw , bt ratio and fer . however , age and duration of diabetes of the mdi group were significantly higher than that of the csii group , and hba1c levels of the csii group were significantly higher than that of the mdi group . simple correlations of the bt ratio or bad / bw with age , sdsbmi , hba1c level and each meal content variable are given in table  2 . in all subjects , there was a positive correlation between age and tdd ( r  =  0.452 , p  =  0.003 ) or sdsbmi and tdd ( r  =  0.320 , p  =  0.041 ) . additionally , there was a positive correlation between bad / bw and fer ( r  =  0.493 , p  =  0.001 ) and a negative correlation between bad / bw and cer ( r  =  0.541 , p  <  0.001 ) . the bod / bw tended to correlate negatively with hba1c level ( r  =  0.281 , p  =  0.075 ) . among patients under 19  years old ( age groups 1 , 2 and 3 ) , there was a positive correlation between bad / bw and sdsbmi ( r  =  0.472 , p  =  0.010 ) or bad / bw and fer ( r  =  0.452 , p  =  0.014 ) . correlations between the dose of insulin and age , sdsbmi , hba1c levels , duration of diabetes or each meal content variable using pearson s productmoment correlations . tdd , total daily insulin doses ; bt ratio , daily basal insulin doses / total daily insulin doses ; bod / bw , daily bolus insulin doses / body weight ; bad / bw , daily basal insulin doses / body weight ; tdd / bw , total daily insulin doses / bw ; per , protein energy ratio of meal ; fer , fat energy ratio of meal ; cer , carbohydrate energy ratio of meal . multiple regression analyses are shown in table  3 . in all subjects , when bad / bw was selected as the dependent variable , fer was obtained as an entered variable ( p  =  0.001 ) . in age group 1 or age group 2 , no value was obtained as an entered variable . in age group 3 , fer was obtained as an entered variable ( p  <  0.001 , standardized coefficient   =  0.844 , adjusted r  =  0.686 ) . in age group 4 , fer was also obtained as an entered variable ( p  =  0.048 , standardized coefficient   =  0.580 , adjusted r  =  0.270 ) . among patients aged 14 or above ( age groups 3 and 4 ) , fer was obtained similarly ( p  <  0.001 , standardized coefficient   =  0.683 , adjusted r  =  0.443 ) . the correlation between fer and bad / bw in age group 3 and 4 ( n  =  25 ) is shown in figure  2 . in the male group or female group , no value was obtained as an entered variable . in the well controlled group , fer was obtained as an entered variable ( p  =  0.003 , standardized coefficient   =  0.631 , adjusted r  =  0.365 ) while none was obtained in the poorly controlled group . independent variables were : gender , age , sdsbmi , hba1c levels , therapy ( mdi or csii ) , and fat energy ratio . in all subjects , age group 3 , age group 4 , age group 3 and 4 or well controlled group , when bad / bw was selected as the dependent variable , bad / bw , daily basal insulin doses / body weight ; fer , fat energy ratio of meal ; well controlled group , hba1c  <  7.0 ; poorly controlled group , hba1c  >  7.0 . the correlation between fer and bad / bw . among patients aged 14 or above ( age group 3 and 4 ) , fer : fat energy ratio of meal , bad / bw : daily basal insulin doses / body weight . in this study , estimation of meal ingredients from photographs taken by patients was chosen as the method for examining meal contents . williamson et  al . reported that estimates of portion sizes related to food selections , plate waste , and food intake correlated highly with actual food weights by both the digital photography and the direct visual estimation method . the correlation coefficient between the estimated amounts of whole meals using digital photography and the actual amounts of meals ranged from 0.89 to 0.94 , indicating a high correlation . reported that a person with considerable knowledge of nutrition , such as a senior nutritionist at a university , could assess nutrient intakes using digital images and that the results of these assessments were accurate . in the present study , three experienced registered dietitians assessed digital images , and their evaluation results were combined to obtain mean values . therefore , given the previous reports , the method used in the present study was considered to be appropriate and to have yielded valid results . furthermore , we asked the subjects to take pictures of food during normal daily life . the nutritional data obtained from the 3  days of food photographs was not so variable day by day . the data of insulin dosage used in this study was also obtained from the same 3  days as the food pictures . therefore , the relationships between the nutritional data and basal insulin dose seems to be reliable . reported that in the ppsg ( the pediatric pump study group ) study conducted in 23 facilities in 9 european countries and israel , the mean bt ratio was 0.48 in 377 patients , with a mean age of 12.9  years , receiving csii therapy and that there were differences among facilities . reported that the mean bt ratio was 0.67 in children with type 1 diabetes mellitus receiving csii therapy in the usa . studies in europe and the usa have often found the bt ratio to be at least 0.50 . studies in japan , on the other hand , have demonstrated bt ratios tending to be lower than those in europe and the usa . the bt ratios were usually below 0.50 in patients receiving basalbolus therapy ( csii or mdi ) , regardless of age , at many japanese facilities . particularly , kuroda reported < 0.30 of bt ratio in japanese type 1 diabetes using csii therapy as inpatients with 5060% cer meals . the bt ratios in europe and the usa , however , are not always high . reported the mean bt ratio to be 0.28 in children with type 1 diabetes mellitus receiving csii therapy in warsaw . therefore , bt ratios are not consistently high in european patients , such that factors other than race and ethnicity are thus considered to be involved . reported bt ratios to correlate positively with age and diabetes duration and to correlate negatively with blood concentrations of cpeptide in type 1 diabetes mellitus patients under 19  years of age in poland . in the present study , however , the bt ratio showed no association with age or disease duration . blood concentrations of cpeptide were not examined in this study , and this relationship thus remains unclear . disease duration and endogenous insulin were thought not to influence bt ratios significantly because patients with disease durations of < 2  years were excluded from this study . many studies worldwide have reported bt ratios , but few have examined associations between bad / bw and other factors . the results of our studies show bad / bw is likely to be associated with sdsbmi in type 1 diabetes mellitus patients of < 19  years of age . this suggests that obesity increases insulin resistance in pediatric type 1 diabetes mellitus patients , as has been observed in other general populations . on the other hand , reported that in 1486 japanese patients with type 1 diabetes mellitus between 16 and 90  years of age , those with higher bmi had higher tdd / bw . although it must be recognized that bad / bw is different from tdd / bw , their results were similar to ours . as to insulin resistance and obesity , reinehr et  al . reported that tdd / body surface area and tdd / ideal body weight correlated more with sdsbmi than tdd / bw in 4124 german patients with type 1 diabetes mellitus . they proposed that glucose uptake occurring mainly in the lean body mass was one of the explanations for this finding , and sdsbmi was associated with a decrease in tdd / bw and an increase in tdd / body surface area and tdd / ideal body weight . the utility of carbohydrate counting for dose adjustment of bolus insulin was recently confirmed , and our department also uses this method for patient education . carbohydrate counting , which allows determination of the doses of bolus insulin based on the amounts of carbohydrate contained in meals , provides very good glycemic control . however , the optimal insulin dosing method with carbohydrate counting when a large amount of protein or fat is ingested has not yet been clearly defined , and no method of achieving this goal has been established . in fact , various studies have focused on identifying an insulin dosing method which allows adjustments for protein and fat intake . according to the results of the national health and nutrition survey conducted in japan in 2008 , the mean fer for the entire japanese population was 0.25 and the mean fer by age group ( 16 , 714 , and 1519  years of age ) were 0.280.29 . the mean per of all three age groups was 0.14 and the mean cer was 0.550.57 . therefore , the present study subjects had slightly higher per and fer and lower cer readings than the mean values for the japanese population as a whole . generally , when a high protein , high fat meal is consumed , blood glucose levels are elevated for at least 5  h afterwards . since the blood glucose elevation due to intake of large amounts of protein and/or fat can be managed by increasing bad , patients , who routinely consume large amounts of protein and fat , are expected to require higher bad . our study revealed that the bad / bw tended to be higher in those with higher fer especially aged 14 or above . this may be considered to explain the aforementioned expectation of increased fat intakes making higher basal insulin doses . to our knowledge , so far , no other studies have shown associations between meal contents and bad . however , this tendency was not seen in the younger age groups . when subjects were divided into four age groups to consider the effect of age , the result of multiple regression analyses was different . while in age groups 1 and 2 ( the age of 13 or younger ) no variable was associated with bad / bw , in age groups 3 and 4 ( the age of 14 or above ) the fer variable was associated with bad / bw . first , because the dose of basal insulin increased as patients grew up , the difference in the older group might easily become significant . all of their parents have received nutritional instruction regarding calories and balanced nutrition at the onset of their child s type 1 diabetes mellitus . according to the guideline of japanese diabetes association , a cer of 5060% , an fer of approximately 30% , and per of approximately 20% were recommended . therefore , it was thought that in patients consuming balanced meals under the management of their parents , variability in cpf ratio ( carbohydrate : protein : fat energy ratio ) would be minimal . while among patients aged 14 or over , an association between bad / bw and fer was shown in the multiple regression analysis . this might be because when the patients grow up and assume responsibility for their own meals , they made their bad requirements adequately . in our study of the multiple regression analysis , dividing the subjects into well and poorly controlled groups , an association between bad / bw and fer was shown in only the well controlled group . this may be because the better controlled patients or their families administer suitable doses of insulin . as described above , the contents of meals , especially carbohydrate amounts , which greatly influence blood glucose levels , and cpf ratio may be an important factor related to bt ratios of insulin doses in mdi . meal contents vary between countries worldwide , and the possibility that the differences in reported bt ratios among facilities are attributable to meal contents can not be ruled out . thus , we calculated cpf ratio based on the report entitled  daily food supply per person in a country published by the fao ( food and agriculture organization of the united nations ) in 2005 , in order to obtain summaries of meal contents . the supplied fat energy / supplied total energy ratios in asian countries were 0.28 ( japan ) , 0.27 ( china ) , and 0.25 ( korea ) . on the other hand , they were 0.30 in poland , 0.36 in germany , 0.41 in france , and 0.41 in the usa . this indicates that fer based on amounts supplied in asian countries , including japan , are lower than those in european countries and the usa . the supplied fat energy / supplied total energy ratio in poland was 0.30 , but , relatively similar to that in japan . as reported by pankowska , people in poland have a lower bt ratio than those in other european countries . however , since these results were calculated based on amounts of food supplied , surveying the meals consumed by each patient , as in our present study , may be necessary to obtain results allowing comparisons among countries . in conclusion , this study demonstrated an association between bad / bw and fer , in particular among the patients aged 14 or above . this may explain the expectation of increased fat intake causing higher basal insulin doses in type 1 diabetes mellitus patients .
abstractaims / introduction :   the daily basal insulin doses / body weight and the daily basal insulin doses / total daily insulin doses of japanese type 1 diabetes mellitus patients are less than those of western type 1 diabetes mellitus patients . 
 it is known that western meals are richer in fat than japanese meals . 
 we speculated that fat intake might be associated with basal insulin dose in type 1 diabetes mellitus patients.materials and methods :   fortyone outpatients with type 1 diabetes mellitus ( 20 males , 21 females , mean age 15.9 ) were enrolled . 
 variables investigated included : gender , sdsbmi , hba1c , duration of diabetes , therapy ( mdi or csii ) , insulin doses and meal contents . 
 meal contents were recorded for 3  days using a digital camera . 
 correlation and multiple regression analyses were performed for all subjects and each age group.results :   the mean daily basal insulin doses / total daily insulin doses was 0.35 . in the multiple regression analysis among all subjects , when daily basal insulin doses / body weight was used as a dependent variable , 
 fat energy ratio of the meal was obtained as an entered variable ( p  =  0.001 ) . 
 this tendency was particularly strong among the patients aged 14 or above ( p  <  0.001 , standardized coefficient   =  0.683).conclusions :   in the type 1 diabetes patients who are aged 14 or above , an association between daily basal insulin doses / body weight and fat energy ratio of meal was suggested . 
 this may explain the aforementioned expectation of increased fat intakes making higher basal insulin doses . 
 ( j diabetes invest , doi : 10.1111/j.20401124.2011.00171.x , 2011 )