racially / ethnically diverse individuals with diabetes diagnosed at age < 18 years and not due to another condition were recruited through clinics , health fairs , and mailings .
one hundred probands with childhood - onset diabetes have participated with their families to date ; this analysis was restricted to those with type 1 diabetes ( n = 79 ) .
examinations were conducted in the morning in the university of chicago general clinical research center or in participants ' homes .
participants aged 18 years and parents of children aged < 18 years provided written consent ; children 1017 years old assented .
current age , pubertal stage , race / ethnicity , and head of household 's education and employment were collected by questionnaire .
pubertal stage was self - assessed with pubic hair tanner diagrams , with missing values ( n = 9 ) imputed using age- , sex- , and race / ethnicity - specific estimates ( 11 ) .
proband race / ethnicity was defined as that reported for 3 grandparents ; if <3 grandparents shared the same race / ethnicity , the proband was of mixed origin . when race / ethnicity was available on <3 grandparents , parental data were used .
if parental data were missing , proband 's self - reported race / ethnicity was used .
height was measured using a stadiometer ; percent body fat ( 10 years old ) and weight were measured with a bioelectrical impedance analyzer scale ( tbf-300a ; tanita , arlington heights , il ) .
bmi was transformed into z scores using the centers for disease control and prevention growth chart ( 20 years old ) ( 12 ) and national health and nutrition examination survey iii ( > 20 years old ) ( 13 ) age - and sex - matched reference data .
proband overweight / obese was defined as a bmi z score 1.04 ( 20 years old ) or bmi 25 kg / m ( > 20 years old ) ( 12,13 ) .
age at diagnosis was abstracted from medical records ; if unavailable , it was self - reported as were frequency of insulin injections and parental diabetes . participants reporting 3 injections per day or use of a pump were defined as receiving an intensive insulin regimen .
type 1 diabetes was defined as having 1 ) no c - peptide ( n = 69 ) or 2 ) detectable c - peptide with < 2 years duration and either positive islet autoantibodies ( gad , insulinoma - associated protein 2 ; n = 10 ) or receiving intensive insulin therapy ( n = 1 ) .
fasting plasma c - peptide was measured in all probands . those with a fasting blood glucose < 150 mg / dl , measured by a glucometer ( onetouch surestep ; lifescan , milpitas , ca ) , also had a stimulated plasma c - peptide measurement 90 min after ingestion of a 6 ml / kg standard nutrient solution ( boost ; novartis nutrition , minneapolis , mn ) .
c - peptide in probands whose fasting glucose was 150 mg / dl was considered stimulated .
c - peptide was determined with a solid - phase , competitive chemiluminescent enzyme immunoassay ( immulite 2000 ; diagnostic products , bad nauheim , germany ) in the university of chicago diabetes research and training center laboratory .
nmol / l , and the intra - assay coefficient of variation ( cv ) was 8% .
absent c - peptide was defined as a fasting , and stimulated if measured , level below the detection limit .
antibodies to radiolabeled recombinant human gad65 ( whole ) and human insulinoma - associated protein 2 ( 349 amino acid cytoplasmic portion ) were quantified by a fluid - phase immunoprecipitation assay .
dyslipidemia was defined by 1 ) use of lipid - lowering medications and/or 2 ) for participants aged 20 years , total cholesterol 200 mg / dl , triglycerides 150 mg / dl , ldl 100 mg / dl , or hdl 59 mg / dl ; and for participants aged < 20 years , total cholesterol 170 mg / dl , triglycerides 150 mg / dl , ldl 110 mg / dl , or hdl 34 mg / dl .
blood pressure was measured three times ; the mean of the second and third values was used .
hypertension was defined by 1 ) use of antihypertensive medications and/or 2 ) systolic blood pressure 140 mmhg and/or diastolic blood pressure 90 mmhg for participants aged 18 years old or systolic and/or diastolic blood pressure exceeding the age- , sex- , and height - specific 95th percentile ( 14 ) for those aged < 18 years .
nephropathy was defined by 1 ) use of ace inhibitors for kidney dysfunction and/or 2 ) an albumin - to - creatinine ratio 30 mg / g .
the michigan neuropathy screening instrument examination was administered by a physician ; participants completed the instrument 's questionnaire .
neuropathy was defined by 1 ) a questionnaire score 5 and/or 2 ) an examination score > 2 ( 15 ) .
fasting serum insulin was measured with a solid - phase , two - site chemiluminescent immunometric assay ( immulite 1000 ; siemens medical solutions diagnostics , los angeles , ca ) by the diabetes research and training center laboratory .
the dca 2000 + analyzer ( bayer healthcare , elkhart , in ) was used to measure a1c in whole blood and urinary albumin and creatinine .
a1c was measured using a latex immunoagglutination inhibition method , and the intra- and interassay cvs were 4.3% .
albumin and creatinine were measured through a benedict - behre chemical reaction , and the intra- and interassay cvs were 6.6% .
total cholesterol and hdl were measured in whole blood by the cholestech ldx system using reflectance photometry ( cholestech , hayward , ca ) .
triglycerides were also measured by the cholestech ldx system by an enzymatic method . for all cholesterol measures ,
c - reactive protein was measured by the university of chicago clinical laboratory using the crplx immunoturbidimetric assay ( roche diagnostics , indianapolis , in ) .
the cot one step cotinine test device ( quiktest usa , boca raton , fl ) was used to detect urine cotinine using a lateral flow chromatographic immunoassay .
serum leptin was determined by the diabetes research and training center laboratory using the human leptin radioimmunoassay kit ( millipore , st .
serum adiponectin was measured using the human adipokine panel a-3 plex assay ( millipore ) by dr .
plasma total and free testosterone and sex hormone  binding globulin ( shbg ) were measured in those aged 10 years old by the university of chicago endocrine laboratory .
total and free testosterone were determined by a solid - phase i radioimmunoassay ( siemens medical solutions diagnostics ) .
insulin resistance in probands was assessed using egdr , a measure derived from clamp studies in 24 nhw adults with long - standing type 1 diabetes using hypertension status , waist - to - hip ratio , and glycemic control ( 5 ) . because hip circumference was not available ,
the comparable equation with waist circumference was provided : egdr ( mg  kg  min ) = 21.158  [ 3.407  hypertension status ( yes = 1 ; no = 0 ) ]  [ 0.090  waist circumference ( cm ) ]  [ 0.551  a1c ( % ) ] .
egdr was highly correlated with clamp - measured insulin resistance ( r = 0.79 ) , and egdr calculated using waist - to - hip ratio or waist circumference was highly correlated ( r = 0.87 ) ( t.j .
the range of clamp - measured glucose disposal rates in the egdr validation study was 3.8 to 13.4 , with a range of 9 to 11 in those with normal insulin resistance ( 5 ) . with the use of fasting insulin and glucose ,
insulin resistance was determined in the parents ( excluding four with type 1 diabetes and two pregnant mothers ) by homeostasis model assessment , version 2.0 ( 17 ) .
analyses were performed in sas ( version 9.1 ; sas institute , cary , nc ) ; statistical tests were considered significant at p < 0.05 .
racial / ethnic groups were compared using t tests for continuous and  tests for categorical variables .
the nonwhite groups ( nhb , other / mixed , and hispanic ) were combined owing to small sample sizes and similar mean egdr .
triglycerides , albumin - to - creatinine ratio , and leptin were log - transformed .
associations of egdr with hypertension , waist circumference , and a1c were not studied because they were used to calculate egdr ; the association with bmi z score was not analyzed because it was highly correlated with waist circumference ( r = 0.92 , p < 0.0001 ) .
the multivariable model estimating egdr was built by first entering all variables with p < 0.15 from the age - adjusted regressions and then using a stepwise approach to remove the nonsignificant covariates .
age - adjusted logistic regression tested the difference in hypertension prevalence by race / ethnicity .
current age , pubertal stage , race / ethnicity , and head of household 's education and employment were collected by questionnaire .
pubertal stage was self - assessed with pubic hair tanner diagrams , with missing values ( n = 9 ) imputed using age- , sex- , and race / ethnicity - specific estimates ( 11 ) .
proband race / ethnicity was defined as that reported for 3 grandparents ; if <3 grandparents shared the same race / ethnicity , the proband was of mixed origin . when race / ethnicity was available on <3 grandparents , parental data were used .
if parental data were missing , proband 's self - reported race / ethnicity was used .
height was measured using a stadiometer ; percent body fat ( 10 years old ) and weight were measured with a bioelectrical impedance analyzer scale ( tbf-300a ; tanita , arlington heights , il ) .
bmi was transformed into z scores using the centers for disease control and prevention growth chart ( 20 years old ) ( 12 ) and national health and nutrition examination survey iii ( > 20 years old ) ( 13 ) age - and sex - matched reference data .
proband overweight / obese was defined as a bmi z score 1.04 ( 20 years old ) or bmi 25 kg / m ( > 20 years old ) ( 12,13 ) .
age at diagnosis was abstracted from medical records ; if unavailable , it was self - reported as were frequency of insulin injections and parental diabetes .
participants reporting 3 injections per day or use of a pump were defined as receiving an intensive insulin regimen .
type 1 diabetes was defined as having 1 ) no c - peptide ( n = 69 ) or 2 ) detectable c - peptide with < 2 years duration and either positive islet autoantibodies ( gad , insulinoma - associated protein 2 ; n = 10 ) or receiving intensive insulin therapy ( n = 1 ) . fasting plasma c - peptide was measured in all probands .
those with a fasting blood glucose < 150 mg / dl , measured by a glucometer ( onetouch surestep ; lifescan , milpitas , ca ) , also had a stimulated plasma c - peptide measurement 90 min after ingestion of a 6 ml / kg standard nutrient solution ( boost ; novartis nutrition , minneapolis , mn ) .
c - peptide in probands whose fasting glucose was 150 mg / dl was considered stimulated .
c - peptide was determined with a solid - phase , competitive chemiluminescent enzyme immunoassay ( immulite 2000 ; diagnostic products , bad nauheim , germany ) in the university of chicago diabetes research and training center laboratory .
nmol / l , and the intra - assay coefficient of variation ( cv ) was 8% .
absent c - peptide was defined as a fasting , and stimulated if measured , level below the detection limit .
antibodies to radiolabeled recombinant human gad65 ( whole ) and human insulinoma - associated protein 2 ( 349 amino acid cytoplasmic portion ) were quantified by a fluid - phase immunoprecipitation assay .
dyslipidemia was defined by 1 ) use of lipid - lowering medications and/or 2 ) for participants aged 20 years , total cholesterol 200 mg / dl , triglycerides 150 mg / dl , ldl 100 mg / dl , or hdl 59 mg / dl ; and for participants aged < 20 years , total cholesterol 170 mg / dl , triglycerides 150 mg / dl , ldl 110 mg / dl , or hdl 34 mg / dl .
blood pressure was measured three times ; the mean of the second and third values was used .
hypertension was defined by 1 ) use of antihypertensive medications and/or 2 ) systolic blood pressure 140 mmhg and/or diastolic blood pressure 90 mmhg for participants aged 18 years old or systolic and/or diastolic blood pressure exceeding the age- , sex- , and height - specific 95th percentile ( 14 ) for those aged < 18 years .
nephropathy was defined by 1 ) use of ace inhibitors for kidney dysfunction and/or 2 ) an albumin - to - creatinine ratio 30 mg / g .
the michigan neuropathy screening instrument examination was administered by a physician ; participants completed the instrument 's questionnaire .
neuropathy was defined by 1 ) a questionnaire score 5 and/or 2 ) an examination score > 2 ( 15 ) .
fasting serum insulin was measured with a solid - phase , two - site chemiluminescent immunometric assay ( immulite 1000 ; siemens medical solutions diagnostics , los angeles , ca ) by the diabetes research and training center laboratory .
the dca 2000 + analyzer ( bayer healthcare , elkhart , in ) was used to measure a1c in whole blood and urinary albumin and creatinine .
a1c was measured using a latex immunoagglutination inhibition method , and the intra- and interassay cvs were 4.3% .
albumin and creatinine were measured through a benedict - behre chemical reaction , and the intra- and interassay cvs were 6.6% .
total cholesterol and hdl were measured in whole blood by the cholestech ldx system using reflectance photometry ( cholestech , hayward , ca ) .
c - reactive protein was measured by the university of chicago clinical laboratory using the crplx immunoturbidimetric assay ( roche diagnostics , indianapolis , in ) .
the cot one step cotinine test device ( quiktest usa , boca raton , fl ) was used to detect urine cotinine using a lateral flow chromatographic immunoassay .
serum leptin was determined by the diabetes research and training center laboratory using the human leptin radioimmunoassay kit ( millipore , st .
serum adiponectin was measured using the human adipokine panel a-3 plex assay ( millipore ) by dr .
plasma total and free testosterone and sex hormone  binding globulin ( shbg ) were measured in those aged 10 years old by the university of chicago endocrine laboratory .
total and free testosterone were determined by a solid - phase i radioimmunoassay ( siemens medical solutions diagnostics ) .
insulin resistance in probands was assessed using egdr , a measure derived from clamp studies in 24 nhw adults with long - standing type 1 diabetes using hypertension status , waist - to - hip ratio , and glycemic control ( 5 ) . because hip circumference was not available ,
the comparable equation with waist circumference was provided : egdr ( mg  kg  min ) = 21.158  [ 3.407  hypertension status ( yes = 1 ; no = 0 ) ]  [ 0.090  waist circumference ( cm ) ]
egdr was highly correlated with clamp - measured insulin resistance ( r = 0.79 ) , and egdr calculated using waist - to - hip ratio or waist circumference was highly correlated ( r = 0.87 ) ( t.j .
the range of clamp - measured glucose disposal rates in the egdr validation study was 3.8 to 13.4 , with a range of 9 to 11 in those with normal insulin resistance ( 5 ) . with the use of fasting insulin and glucose ,
insulin resistance was determined in the parents ( excluding four with type 1 diabetes and two pregnant mothers ) by homeostasis model assessment , version 2.0 ( 17 ) .
current age , pubertal stage , race / ethnicity , and head of household 's education and employment were collected by questionnaire .
pubertal stage was self - assessed with pubic hair tanner diagrams , with missing values ( n = 9 ) imputed using age- , sex- , and race / ethnicity - specific estimates ( 11 ) .
proband race / ethnicity was defined as that reported for 3 grandparents ; if <3 grandparents shared the same race / ethnicity , the proband was of mixed origin . when race / ethnicity was available on <3 grandparents , parental data were used .
if parental data were missing , proband 's self - reported race / ethnicity was used .
height was measured using a stadiometer ; percent body fat ( 10 years old ) and weight were measured with a bioelectrical impedance analyzer scale ( tbf-300a ; tanita , arlington heights , il ) .
bmi was transformed into z scores using the centers for disease control and prevention growth chart ( 20 years old ) ( 12 ) and national health and nutrition examination survey iii ( > 20 years old ) ( 13 ) age - and sex - matched reference data .
proband overweight / obese was defined as a bmi z score 1.04 ( 20 years old ) or bmi 25 kg / m ( > 20 years old ) ( 12,13 ) .
age at diagnosis was abstracted from medical records ; if unavailable , it was self - reported as were frequency of insulin injections and parental diabetes .
participants reporting 3 injections per day or use of a pump were defined as receiving an intensive insulin regimen .
type 1 diabetes was defined as having 1 ) no c - peptide ( n = 69 ) or 2 ) detectable c - peptide with < 2 years duration and either positive islet autoantibodies ( gad , insulinoma - associated protein 2 ; n = 10 ) or receiving intensive insulin therapy ( n = 1 ) .
those with a fasting blood glucose < 150 mg / dl , measured by a glucometer ( onetouch surestep ; lifescan , milpitas , ca ) , also had a stimulated plasma c - peptide measurement 90 min after ingestion of a 6 ml / kg standard nutrient solution ( boost ; novartis nutrition , minneapolis , mn ) .
c - peptide in probands whose fasting glucose was 150 mg / dl was considered stimulated .
c - peptide was determined with a solid - phase , competitive chemiluminescent enzyme immunoassay ( immulite 2000 ; diagnostic products , bad nauheim , germany ) in the university of chicago diabetes research and training center laboratory .
nmol / l , and the intra - assay coefficient of variation ( cv ) was 8% .
absent c - peptide was defined as a fasting , and stimulated if measured , level below the detection limit .
antibodies to radiolabeled recombinant human gad65 ( whole ) and human insulinoma - associated protein 2 ( 349 amino acid cytoplasmic portion ) were quantified by a fluid - phase immunoprecipitation assay .
dyslipidemia was defined by 1 ) use of lipid - lowering medications and/or 2 ) for participants aged 20 years , total cholesterol 200 mg / dl , triglycerides 150 mg / dl , ldl 100 mg / dl , or hdl 59 mg / dl ; and for participants aged < 20 years , total cholesterol 170 mg / dl , triglycerides 150 mg / dl , ldl 110 mg / dl , or hdl 34 mg / dl .
blood pressure was measured three times ; the mean of the second and third values was used .
hypertension was defined by 1 ) use of antihypertensive medications and/or 2 ) systolic blood pressure 140 mmhg and/or diastolic blood pressure 90 mmhg for participants aged 18 years old or systolic and/or diastolic blood pressure exceeding the age- , sex- , and height - specific 95th percentile ( 14 ) for those aged < 18 years .
nephropathy was defined by 1 ) use of ace inhibitors for kidney dysfunction and/or 2 ) an albumin - to - creatinine ratio 30 mg / g .
the michigan neuropathy screening instrument examination was administered by a physician ; participants completed the instrument 's questionnaire .
neuropathy was defined by 1 ) a questionnaire score 5 and/or 2 ) an examination score > 2 ( 15 ) .
fasting serum insulin was measured with a solid - phase , two - site chemiluminescent immunometric assay ( immulite 1000 ; siemens medical solutions diagnostics , los angeles , ca ) by the diabetes research and training center laboratory .
the dca 2000 + analyzer ( bayer healthcare , elkhart , in ) was used to measure a1c in whole blood and urinary albumin and creatinine .
a1c was measured using a latex immunoagglutination inhibition method , and the intra- and interassay cvs were 4.3% .
albumin and creatinine were measured through a benedict - behre chemical reaction , and the intra- and interassay cvs were 6.6% .
total cholesterol and hdl were measured in whole blood by the cholestech ldx system using reflectance photometry ( cholestech , hayward , ca ) .
triglycerides were also measured by the cholestech ldx system by an enzymatic method . for all cholesterol measures ,
c - reactive protein was measured by the university of chicago clinical laboratory using the crplx immunoturbidimetric assay ( roche diagnostics , indianapolis , in ) .
the cot one step cotinine test device ( quiktest usa , boca raton , fl ) was used to detect urine cotinine using a lateral flow chromatographic immunoassay .
serum leptin was determined by the diabetes research and training center laboratory using the human leptin radioimmunoassay kit ( millipore , st .
serum adiponectin was measured using the human adipokine panel a-3 plex assay ( millipore ) by dr .
plasma total and free testosterone and sex hormone  binding globulin ( shbg ) were measured in those aged 10 years old by the university of chicago endocrine laboratory .
total and free testosterone were determined by a solid - phase i radioimmunoassay ( siemens medical solutions diagnostics ) .
insulin resistance in probands was assessed using egdr , a measure derived from clamp studies in 24 nhw adults with long - standing type 1 diabetes using hypertension status , waist - to - hip ratio , and glycemic control ( 5 ) . because hip circumference was not available ,
the comparable equation with waist circumference was provided : egdr ( mg  kg  min ) = 21.158  [ 3.407  hypertension status ( yes = 1 ; no = 0 ) ]  [ 0.090  waist circumference ( cm ) ]  [ 0.551  a1c ( % ) ] .
egdr was highly correlated with clamp - measured insulin resistance ( r = 0.79 ) , and egdr calculated using waist - to - hip ratio or waist circumference was highly correlated ( r = 0.87 ) ( t.j .
the range of clamp - measured glucose disposal rates in the egdr validation study was 3.8 to 13.4 , with a range of 9 to 11 in those with normal insulin resistance ( 5 ) . with the use of fasting insulin and glucose ,
insulin resistance was determined in the parents ( excluding four with type 1 diabetes and two pregnant mothers ) by homeostasis model assessment , version 2.0 ( 17 ) .
analyses were performed in sas ( version 9.1 ; sas institute , cary , nc ) ; statistical tests were considered significant at p < 0.05 .
racial / ethnic groups were compared using t tests for continuous and  tests for categorical variables .
the nonwhite groups ( nhb , other / mixed , and hispanic ) were combined owing to small sample sizes and similar mean egdr .
triglycerides , albumin - to - creatinine ratio , and leptin were log - transformed .
associations of egdr with hypertension , waist circumference , and a1c were not studied because they were used to calculate egdr ; the association with bmi z score was not analyzed because it was highly correlated with waist circumference ( r = 0.92 , p < 0.0001 ) .
the multivariable model estimating egdr was built by first entering all variables with p < 0.15 from the age - adjusted regressions and then using a stepwise approach to remove the nonsignificant covariates .
age - adjusted logistic regression tested the difference in hypertension prevalence by race / ethnicity .
for the 79 probands ( table 1 ) , mean current age was 13.5 years ( range 3.232.5 ) ; 32.9% were nhw , 46.8% were nhb , 7.6% were other / mixed , and 12.7% were hispanic .
mean disease duration was 5.7 years ( 0.119.9 ) , mean current a1c was 9.1% , and 69.6% were receiving an intensive insulin regimen .
only six probands were overweight / obese ( one nhw , four nhb , and one other / mixed ) .
a large proportion had complications including dyslipidemia ( 53.2% ) and hypertension ( 21.5% ) .
more than two - thirds had at least one obese parent , and 14.5% had at least one parent who self - reported diabetes .
current age had an inverse association with egdr : egdr ( mg  kg  min ) = 12.51  [ 0.26  age ( years ) ] ( p < 0.0001 ) .
diabetes duration also had an inverse association with egdr : egdr ( mg  kg  min ) = 10.15  [ 0.19  duration ( years ) ] ( p = 0.004 ) . however , the relationship with diabetes duration was not significant after adjusting for age .
race / ethnicity was significantly associated with egdr even after adjustment for age ; compared with nhw , egdr was significantly lower among nonwhites [ mean difference (  ) = 1.83 , p = 0.0006 ]
. associations of egdr with demographic , anthropometric , diabetes , clinical , and hormonal characteristics in probands with type 1 diabetes n = 79 .
with adjustment for age , egdr had a significant negative association with percent body fat ( table 2 ) .
probands with at least one obese parent had significantly lower egdr levels than those with no obese parent (  = 2.42 , p = 0.0001 ) ; further adjustment for probands ' percent body fat did not attenuate this association .
probands with at least one insulin - resistant parent also had significantly lower egdr than those with no insulin - resistant parent (  = 1.79 , p = 0.03 ) ; however , parental self - reported diabetes status was not associated with proband egdr .
egdr was positively associated with hdl and negatively associated with triglycerides and albumin - to - creatinine ratio .
participants with acanthosis nigricans and those with elevated c - reactive protein had significantly lower egdr compared with those without (  = 2.06 , p = 0.0002 , and  = 1.84 , p = 0.04 , respectively ) . in those with body fat determined ( 10 years old , n = 57 ) , the association of egdr with c - reactive protein was also significant , but the relationship became nonsignificant after adjustment for body fat .
both leptin and adiponectin were negatively associated with egdr , but after controlling for age , adiponectin was no longer significant ( table 2 ) .
further , for the subgroup of probands with body fat determined ( n = 51 ) , leptin was negatively associated with egdr , but subsequent adjustment for percent body fat attenuated this association .
in stratified analyses , shbg was positively associated with egdr in both sexes and remained significant in women after controlling for age . among all probands
, there was a significant age- and sex - adjusted positive association between egdr and shbg ( regression coefficient = 0.96 mg  kg min rise in egdr per 10 nmol / l increase in shbg , p = 0.0001 ) ; additional adjustment for proband percent body fat did not change this association .
in multivariable analysis ( table 3 ) , lower egdr was significantly associated with older age , nonwhite race / ethnicity , and acanthosis .
when hdl was included , resulting in a smaller sample size , these associations remained significant .
the potential confounding effects of probands ' percent body fat , parental obesity , and parental insulin resistance on these associations were examined and found not to occur nor did race / ethnicity modify the associations of egdr with these factors .
variables entered into the model : current age , race / ethnicity , head of household education , percent body fat , parental obesity , parental insulin resistance , hdl , triglycerides , albumin - to - creatinine ratio , acanthosis , elevated c - reactive protein , positive cotinine , sleep duration , and shbg . whether the racial / ethnic variation in egdr was driven by differences in the components used to calculate egdr was explored . with adjustment for age , compared with nhw participants , nonwhites had significantly higher a1c and a trend for larger waist circumference ( 9.7 vs. 7.9% , p = 0.0005 , and 72.2 vs. 68.2 cm , p = 0.10 , respectively ; estimates at mean age of 13.5 years ) , and a trend toward a higher prevalence of hypertension ( 26.4 vs. 11.5% , odds ratio 3.1 , p = 0.10 ) .
insulin resistance is an important component of type 1 diabetes ( 2 ) . to our knowledge , this is the first study to show that racial / ethnic differences in insulin resistance , as measured by egdr , exist in this group .
furthermore , this variation was observed in a sample of young individuals with short diabetes duration and normal adiposity , suggesting that racial / ethnic differences are present early in the disease course .
the current results are consistent with previous research in healthy individuals and in those with type 2 diabetes of whom nonwhite groups were generally more insulin resistant . specifically , nondiabetic african american and hispanic adults were more insulin resistant than nondiabetic nhw adults , using a frequently sampled intravenous glucose tolerance test with minimal model analysis ( 8) . for adults with type 2 diabetes , african americans , but not hispanics , were more insulin resistant than nhw ( 1 )
. the picture may be more complicated in adolescence , because puberty is an insulin - resistant state ( 10 ) .
one study demonstrated that mexican american , but not black , children were more insulin - resistant than nhw youth as measured by homeostasis model assessment ( 9 ) , whereas another study using the clamp method found that insulin resistance was increased in black but not white participants between 11 and 19 years of age ( 10 ) .
our results demonstrating trends for racial / ethnic differences in the egdr components are also consistent with the literature , with minorities demonstrating poorer outcomes .
for example , african american children with type 1 diabetes have worse glycemic control than white children with diabetes ( 18 ) . with regard to adiposity ,
a higher percentage of mexican - american and black adolescents are overweight / obese compared with nhw adolescents ( 9 ) .
the national health and nutrition examination survey iii also found that african american adult women with type 2 diabetes have a higher bmi than nhw women with diabetes ( 19 ) .
last , hypertension is more prevalent in african american adults than in nhw and mexican american adults , both with and without type 2 diabetes ( 20 ) .
for example , higher insulin resistance is related to older age and longer disease duration ( 6 ) .
the authors found similar relationships , but the association with age was stronger and duration was no longer significant after adjustment for age . family history of type 2 diabetes has been shown to be associated with greater insulin resistance in those with type 1 diabetes ( 5 ) . in the current study , there was no association with parental history of diabetes , which was based on self - report .
however , parental obesity and parental insulin resistance , which were directly measured in the current study and are risk factors for diabetes , were related to greater proband age - adjusted insulin resistance .
this association was independent of the probands ' adiposity , indicating that other familial characteristics in addition to factors affecting probands ' body composition ( e.g. , genetic predisposition ) may influence their insulin resistance .
lower levels of shbg were also significantly associated with greater insulin resistance in age - adjusted analysis .
this finding is consistent with basic science ( 21 ) and clinical research ( 22 ) demonstrating a negative association between insulin and shbg levels , such that the greater the level of insulin resistance in an individual with type 1 diabetes is , the higher is the insulin dose required to meet physiological requirements and the lower the hepatic production of shbg .
these results suggest that the derived measure of insulin resistance , egdr , is indeed measuring insulin resistance in those with type 1 diabetes .
the risk of micro - and macrovascular complications is elevated for individuals with type 1 diabetes who have insulin resistance .
for example , greater insulin resistance is associated with the development of nephropathy ( 3,6 ) , neuropathy ( 7 ) , and elevated lipids ( 6 ) . in the current study ,
it could be argued that these relationships may be capturing the well - established associations of diabetes complications with the components used to calculate egdr , specifically suboptimal glycemic control and/or hypertension .
however , previous research in nhw adults with long - standing type 1 diabetes showed that insulin resistance as measured by egdr more strongly predicted overt diabetic nephropathy than did glycemia or blood pressure ( 23 ) .
egdr is a derived measure of insulin resistance , and clamp techniques are needed to confirm our results .
however , because egdr is noninvasive and strongly correlated with clamp - measured insulin resistance , it is useful for population - based studies , similar to the numerous surrogate measures of insulin resistance that are commonly used in studies of type 2 diabetic and nondiabetic groups .
we demonstrated for the first time associations of proband insulin resistance with parental obesity and parental insulin resistance , although there may have been limited power to confirm the associations in the multivariable model .
limited sample size may also explain the lack of a significant difference in insulin resistance by neuropathy status , although the magnitude of the difference was small .
last , because we combined nonwhite groups owing to small sample sizes and similar egdr , we may have limited the ability to detect interactions by race / ethnicity .
the research had a number of strengths , most importantly that it is the first study of type 1 diabetes , to our knowledge , to examine insulin resistance using a racially / ethnically diverse sample .
we were also able to evaluate and adjust for confounders in the multivariable model to estimate the independent association of race / ethnicity with insulin resistance .
the greater insulin resistance observed in nonwhites with type 1 diabetes may help clarify the well - documented gaps in diabetes outcomes for underserved minorities .
insulin resistance is associated with a spectrum of poor health outcomes ; thus , the greater insulin resistance in minorities with type 1 diabetes may explain their higher incidence of diabetes - related complications compared with nhw ( 24 ) .
future research is needed to determine which factors contribute to racial / ethnic differences in insulin resistance in this group , such as disparities in diabetes care , differences in behaviors , environmental factors , or physiological processes , or simply residual confounding . understanding which modifiable factors prevent insulin resistance and
then targeting interventions to those groups most at risk will help address the public health burden of type 1 diabetes and its complications in minority populations . in summary , insulin resistance as estimated by egdr was greater in minorities with type 1 diabetes than in nhw probands . because there exists a strong association between insulin resistance and poor health outcomes in diabetes , the search for effective interventions to improve insulin resistance in minorities with type 1 diabetes must become a priority .
 objectiveinsulin resistance is greater in racial / ethnic minorities than in non - hispanic whites ( nhws ) for those with and without type 2 diabetes . because previous research on insulin resistance in type 1 diabetes was limited to nhws , racial / ethnic variation in an estimated measure of insulin resistance in type 1 diabetes was determined.research design and methodsthe sample included 79 individuals with type 1 diabetes diagnosed at age < 18 years ( 32.9% nhws , 46.8% non - hispanic black [ nhb ] , 7.6% other / mixed , and 12.7% hispanic ) and their families . 
 estimated glucose disposal rate ( egdr ) ( milligrams per kilogram per minute ; a lower egdr indicates greater insulin resistance ) was calculated using a1c , waist circumference , and hypertension status.resultsmean current age was 13.5 years ( range 3.232.5 ) and diabetes duration was 5.7 years ( 0.119.9 ) . 
 egdr was inversely associated with age . compared with that in nhws , 
 age - adjusted egdr was significantly lower among nonwhites ( nhb , other / mixed , and hispanic :  = 1.83 , p = 0.0006 ) . 
 age - adjusted egdr was negatively associated with body fat , triglycerides , urinary albumin / creatinine , acanthosis nigricans , parental obesity , and parental insulin resistance and positively related to hdl and sex hormone  binding globulin . in multivariable analysis , 
 lower egdr was significantly associated with older age , nonwhite race / ethnicity , acanthosis , and lower hdl.conclusionsminorities with type 1 diabetes are significantly more insulin resistant , as measured by egdr , than nhws . exploring potential mechanisms , including disparities in care and/or physiological variation , 
 may contribute to preventing racial / ethnic differences in insulin resistance  associated outcomes . 