in both diabetic and non - diabetic patients , albuminuria has been recognised as an important renal and cardiovascular risk factor .
although , using chemical methods , albuminuria had been detected in patients without primary renal disease more than 100  years ago , it was only after the introduction of immune detection methods   and the recognition that albuminuria is a predictor of diabetic nephropathy in type 1 and type 2 diabetes [ 4 , 5 ] that there was an explosive growth of information in this field .
the issue whether there is a safe threshold value of albuminuria has recently provoked intense discussion , mainly because in both non - diabetic   and diabetic   patients , urinary albumin concentrations in the upper normal range have been found to predict both cardiovascular   and renal plus cardiovascular events   in high risk   and low risk   populations . for these and other reasons
it has been proposed by some authors to abandon microalbuminuria as a diagnostic category and to treat urinary albumin excretion ( uae ) as a continuous variable , much like bp or serum cholesterol concentration .
a great number of past and recent studies have evaluated the evolution of uae from normoalbuminuria to microalbuminuria and its correlates in adolescent [ 1012 ] and adult [ 13 , 14 ] type 1 diabetic patients .
information on type 2 diabetic patients is scarcer and is available only for some small cohorts .
the roadmap ( randomised olmesartan and diabetes microalbuminuria prevention ) study   started in 2004 and provided a unique opportunity to investigate the factors which correlate with albumin excretion rates across the range of normoalbuminuric values in a large cohort of type 2 diabetic patients .
knowledge of these factors is of interest because albuminuria is correlated with cardiovascular and renal risk .
it is the goal of the roadmap study to provide further information on the selection of strategies for primary prevention of diabetic nephropathy . in normoalbuminuric type 2
diabetic patients , it has already been shown that an ace inhibitor reduces the risk of de novo onset of microalbuminuria , but , as recently emphasised in a cochrane review , there is a deficit of information on angiotensin receptor blockers ( arbs ) .
the aim of the roadmap study is to provide evidence of whether or not it is possible to prevent the development of microalbuminuria by administration of the arb olmesartan medoxomil . in the present study ,
we analysed the baseline albuminuria levels in the roadmap cohort and determined which factors correlate with the degree of albuminuria within the so - called normoalbuminuric range .
the design of the roadmap study has been described in detail previously . in the following details relating to the baseline data
study design and organisation roadmap is a randomised , double - blind , placebo - controlled , parallel - group , multicentre phase 3 study that is being conducted in 262 collaborating centres in 19 european countries . the study protocol , which complies with the principles of good clinical practice and the declaration of helsinki , has been approved by the relevant ethics committee at each participating centre .
study population the study has recruited 4,449 white patients ( 2,054 male and 2,395 female ; age range , 1875  years ) with : type 2 diabetes ( fasting plasma glucose 7.0  mmol / l and hba1c  6.5% , or treatment for diabetes ) ; normoalbuminuria ( 35  mg [ women ] or 25  mg [ men ] albumin / g urinary creatinine ) ; and at least one additional cardiovascular risk factor , including a lipid disorder defined as > 5.2  mmol / l cholesterol or statin treatment , hdl - cholesterol < 1.04  mmol / l , triacylglycerol > 1.70 
mmol / l , high systolic bp ( sbp ) ( 130  mmhg ) and diastolic bp ( dbp ) ( 80  mmhg ) or antihypertensive medication , obesity ( bmi    28 
m / kg ) , high waist circumference ( > 102  cm [ men ] , > 88  cm [ women ] ) or smoking more than five cigarettes per day.exclusion criteria included documented renal and/or renal  vascular disease , estimated gfr ( egfr ) < 60  ml  min  m , recent cardiovascular event , severe hypertension ( sbp  >  200  mmhg and/or dbp  >  110  mmhg ) and recent ( < 26  weeks ) treatment with arbs or ace inhibitors .
patient recruitment commenced in 2004 and was completed in the first half of 2006.office bp measurements were performed between 06:00 and 11:00  hours as trough readings and made three times in the sitting position ( with mean calculated ) and once standing , using standardised oscillometric omron hem-907 bp monitors ( omron , stuttgart , germany).in 1,234 patients , 24  h ambulatory bp monitoring ( abpm ) was performed at baseline visit , using boso tm-2430 ambulatory bp measurement devices ( boso , jungingen , germany ) .
( 07:0022:00  hours ) measurements were performed every 15  min and during the night ( 22:0007:00  hours ) every 30  min.the urinary albumin / creatinine ratio ( uacr ) and all other laboratory values were determined in a central laboratory ( crl - medinet , breda , the netherlands ) within 24  h after obtaining the urine and blood samples from the patient .
urinary albumin was measured using immunoturbidimetry ( roche , basel , switzerland).in a screening visit the potential eligibility for the study was established by determining the uacr by morning spot urine testing . after a pre - randomisation phase ( maximum duration 4  weeks ) during which normoalbuminuria was confirmed by two additional independent morning spot urine tests . for the analysis of baseline
statistical analysis baseline characteristics were analysed by the following descriptive statistics : for dichotomous and categorical variables absolute and relative frequencies ( counts and percents ) were calculated , whereby the denominator for per cents is defined as the number of patients with non - missing values.comprehensive data summaries were performed by means of sample characteristics for all continuous variables ( n ; missing n ; arithmetic mean ; sd ; minimum , lower quartile , median , upper quartile , maximum and geometric mean if appropriate).correlations with albuminuria at screening were calculated for continuous variables by means of spearman rank correlation coefficients ( univariate and multivariate analysis ; multivariate regression model with stepwise selection for loge albumin / creatinine ratio ) and for categorical variables by means of a wilcoxon rank sums test ( two - sided test , normal approximation of test statistics of this non - parametric test ) . 

\documentclass[12pt]{minimal } 
				 \usepackage{amsmath } 
				 \usepackage{wasysym } 
				 \usepackage{amsfonts } 
				 \usepackage{amssymb } 
				 \usepackage{amsbsy } 
				 \usepackage{mathrsfs } 
				 \usepackage{upgreek } 
				 \setlength{\oddsidemargin}{-69pt } 
				 \begin{document}$$ { \text{egfr}}\left ( { { \text{ml}}\;{\text{mi}}{{\text{n}}^ { - { \text{1}}}}{\text{1}}.{\text{73}}\;{{\text{m}}^ { - { \text{2 } } } } } \right ) = { \text{16442 } } \times { \left ( { \text{pcr } } \right)^ { - { \text{1}}.{\text{154 } } } } \times { \left ( { { \text{age}}\;{\text{in}}\;{\text{years } } } \right)^ { - 0.{\text{2}}0{\text{3}}}}\left ( { \times 0.{\text{742}}\;{\text{for}}\;{\text{female}}\;{\text{patients } } } \right ) , $ $ \end{document}where pcr is serum creatinine measured in micromole per litre .
a total of 4,449 type 2 diabetic patients were included in the study : 90.3% of the patients had hypertension , defined as a bp  >  130/80  mmhg or antihypertensive treatment ; 67.5% of patients were receiving antihypertensive treatment ; 71.6% had lipid disorders .
table  1patient data at baselinecharacteristictotaltotal4,449women , n ( % ) 2,395 ( 53.8)age ( years)57.7    8.7 ( 58)known duration of diabetes ( years)6.1    6.0 ( 4.3)insulin treatment , n ( % ) 821 ( 18.5%)oral hypoglycaemic agents3,752 ( 84.3)hba1c ( % ) 7.6    1.6 ( 7.3)fasting blood glucose ( mmol / l)9.1    3.1 ( 8.4)sbp ( mmhg)140.8    16.3 ( 140.0)dbp ( mmhg)84.0    9.8 ( 84.0)bmi ( kg / m)31.0    4.9 ( 30.5)central obesity , n ( % ) 3,181 ( 71.5)metabolic syndrome , n ( % ) 3,528 ( 79.3)current smokers , n ( % ) 831 ( 18.7)egfr ( ml  min 1.73  m)84.5    16.8 ( 83.8)haemoglobin ( g / l)142    13 ( 141)triacylglycerol ( mmol / l)2.1    1.3 ( 1.8)total cholesterol ( mmol / l)5.3    1.1 ( 5.2)ldl - cholesterol ( mmol / l)3.2    0.9 ( 3.1)hdl - cholesterol ( mmol / l)1.2    0.3 ( 1.2)uric acid ( mol / l)321    83 ( 321)known family history of diabetes , n ( % ) 2,194 ( 49.3)known family history of cv events , n ( % ) 1,678 ( 37.7)values are meanssd ( median ) for continuous variables , or n ( % ) for categorical variableshigh waist circumference : > 102  cm in men , > 88  cm in womenncep atp iii criteriamore than five cigarettes per daycv , cardiovascular patient data at baseline values are meanssd ( median ) for continuous variables , or n ( % ) for categorical variables high waist circumference : > 102  cm in men , > 88  cm in women ncep atp iii criteria more than five cigarettes per day albuminuria at screening in these patients the albumin / creatinine ratio in morning spot urine tests was loge normally distributed with a median of 0.44  mg / mmol creatinine ( interquartile range 0.280.81 ; fig .  1 ) . in men ,
the median was 0.41  mg / mmol creatinine ( interquartile range 0.240.75 , mean 0.58    0.78 , geometric mean 0.43 ) and in women the median was 0.46  mg / mmol creatinine ( interquartile range 0.310.88 , mean 0.67    0.54 , geometric mean 0.52 ) . 

1relationship of uacr with quintiles of night - time sbp ( a ) , hba1c ( b ) and egfr ( c)the median uncorrected albumin concentration in morning spot urine tests in men was 4.2  mg / ml ( interquartile range 2.07.7 , mean 6.11    10.26 , geometric mean 4.2 ) and in women 3.2  mg / ml ( interquartile range 1.56.2 , mean 5.04    5.27 , geometric mean 3.6 ) . the albumin / creatinine ratio is higher in women , as expected , because of the higher uacr exclusion values for female patients ( 3.96 mg / mmol ) than for men ( 2.83  mg / mmol ) ; however the absolute uncorrected albumin concentration is lower in women as a result of markedly lower urinary creatinine concentrations in women .
relationship of uacr with quintiles of night - time sbp ( a ) , hba1c ( b ) and egfr ( c ) ambulatory bp ( holter monitoring ) in a sub - cohort of patients the values of 24  h abpm prior to taking the study medication were available in a sub - cohort of 1,234 of the 4,449 patients ( 567 men , 667 women ) .
the average bp was 139.6/81.5  mmhg , confirming the results obtained in the office bp cohort . 

table  2twenty - four hour data from abpmreadingvalue ( n  =  1,234)24  h sbp139.6    15.4 ( 138.9)24  h dbp81.5    8.1 ( 81.1)daytime sbp143.6    15.6 ( 143.4)daytime dbp84.3    8.5 ( 83.8)night - time sbp133.8    17.9 ( 131.7)night - time dbp77.4    9.4 ( 6.9)24  h pulse pressure58.1    10.3 ( 57.6)daytime pulse pressure59.3    10.7 ( 59.0)night - time pulse pressure56.5    11.7 ( 55.1)mean daytime sbp minus mean night - time sbp9.7    12.1 ( 10.0)mean daytime dbp minus mean night - time dbp6.9    7.3 ( 6.9)values are means  sd ( median )
twenty - four hour data from abpm values are means  sd ( median ) correlation of albuminuria with continuous variables the correlations for different continuous variables were calculated .
the strongest correlation was observed for night - time sbp and hba1c levels ( table  3 and fig . 
multivariate analysis in the total cohort and in the sub - cohort of patients with abpm confirmed that hba1c and sbp had the best correlation with uacr ( tables  4 and 5 ) . 

table  3spearman rank correlation coefficients ( rs ) by univariate analysis with uacr ( morning spot urine ) as the dependent variablevariablersp valuenight - time sbp0.19<0.0001hba1c0.18<0.0001mean 24  h sbp0.16<0.0001fasting glucose0.16<0.0001night - time dbp0.12<0.0001mean 24  h dbp*0.110.0001office sbp ( sitting)0.11<0.0001office sbp ( standing)0.10<0.0001egfr0.10<0.0001haemoglobin0.10<0.0001triacylglycerols0.09<0.0001office pulse pressure ( amplitude)0.08<0.0001uric acid0.08<0.0001duration of diabetes0.07<0.0001office dbp ( standing)0.07<0.0001office dbp ( sitting)0.06<0.0001bmi0.06<0.0001total cholesterol0.050.0014no univariate spearman correlation to : abpm sbp variability ( maximumminimum during 24  h period ) , ldl - cholesterol , hdl - cholesterol or neutrophil countsabpm ( holter monitoring ) data in sub - cohort of 1,234 patientstable  4multivariate regression model with stepwise selection of loge uacrordervariablepartial rp valueregression coefficient1hba1c0.0344<0.00010.054192sex ( females higher ) ( coded 0=male , 1=female)0.0137<0.00010.166933office sbp ( sitting)0.0126<0.00010.004224egfr0.0123<0.00010.005745triacylglycerols0.0047<0.00010.034306haemoglobin0.0034<0.00010.004207family history of diabetes0.00280.00020.066268age0.00230.00100.005339heart rate ( sitting)0.00200.00210.0031310antihypertensive treatment0.00210.00150.0812911smoking status ( ordinally coded 0=non - smoker , 1=ex - smoker , 2=smoker)0.00190.00270.0445112fasting glucose0.00090.03260.0103413hdl - cholesterol0.00090.04090.0790714family history of cvd0.00080.04360.04354variables with a positive sign for the regression coefficient , increasing albuminuria ; with a negative sign , decreasing albuminuriacvd , cardiovascular diseasetable  5multivariate regression model with stepwise selection of loge uacr in the sub - cohort with abpm ( n  =  1,234)ordervariablepartial rp valueregression coefficient1hba1c0.0484<0.00010.080132abpm night - time sbp0.0267<0.00010.004053office sbp ( sitting)0.01030.00020.004844family history of diabetes0.00940.00040.142845antihypertensive treatment0.00620.00370.145486egfr0.00610.00390.004057sex ( females higher ) ( coded 0=male , 1=female)0.00470.01130.115028duration of type 2 diabetes0.00420.01590.000639standing minus sitting office dbp0.00310.03970.0076810standing minus sitting office heart rate0.00310.03720.00815 spearman rank correlation coefficients ( rs ) by univariate analysis with uacr ( morning spot urine ) as the dependent variable no univariate spearman correlation to : abpm sbp variability ( maximumminimum during 24  h period ) , ldl - cholesterol , hdl - cholesterol or neutrophil counts abpm ( holter monitoring ) data in sub - cohort of 1,234 patients multivariate regression model with stepwise selection of loge uacr variables with a positive sign for the regression coefficient , increasing albuminuria ; with a negative sign , decreasing albuminuria cvd , cardiovascular disease multivariate regression model with stepwise selection of loge uacr in the sub - cohort with abpm ( n  =  1,234 ) correlation of albuminuria with categorical variables the correlations for a set of categorical variables were calculated .
a highly significant correlation existed between the degree of uacr and variables of the metabolic syndrome , bp and female sex ( table  6 ) . 

table  6correlation of uacr with categorical variablesvariableeffect on albuminuriap valueincreased waist circumferencehigher<0.0001  men > 102  cmhigher0.0171  women > 88  cmhighernsmetabolic syndrome ( yes ) ( ncep - atp - iii)higher<0.0001female sexhigher<0.0001family history of diabeteslower0.0068family history of cvdlower0.0252antihypertensive medicationhigher<0.0001amlodipine treatmenthigher<0.0001insulin treatmenthigher0.0280office sbp > 140  mmhg or dbp > 90  mmhghigher<0.0001office sbp > 130  mmhg or dbp > 85  mmhghigher<0.0001smoking : male ex - smokers vs non - smokers and smokershigher0.0002categorical factors that were not significant included : family history of renal disease , family history of hypertension , current use of aspirin or statins , ethnic origin , smoking in womentwo - sided wilcoxon rank sum test ; normal approximation of test statisticscvd , cardiovascular disease correlation of uacr with categorical variables categorical factors that were not significant included : family history of renal disease , family history of hypertension , current use of aspirin or statins , ethnic origin , smoking in women two - sided wilcoxon rank sum test ; normal approximation of test statistics cvd , cardiovascular disease night - time bp as determinant of albuminuria as the night - time bp showed a high correlation in the uni- and multivariate analysis ( abpm sub - cohort ) , the effect of bp changes from day to night were analysed .
the mean uacr was 0.63    0.53  mg / mmol in patients with an increased bp during the night and 0.54    0.44  mg / mmol in patients with an inverted bp profile ( i.e. increased bp during the day ; table  7 ) . 

table  7uacr ( mg / mmol ) in patients ( abpm sub - cohort ) with night - time sbp lower or higher than daytime sbpdatasbp at night sbp in day
( n  =  1,001)sbp at night sbp in day ( n  =  229)total ( n  =  1,230)meansd0.54    0.440.63    0.530.55   
0.46q1/median / q30.26/0.37/0.680.31/0.45/0.820.27/0.42/0.68minimum to maximum0.113.420.114.030.114.03p  =  0.0076 vs sbp at night sbp in dayq , quartile uacr ( mg / mmol ) in patients ( abpm sub - cohort ) with night - time sbp lower or higher than daytime sbp p  =  0.0076 vs sbp at night sbp in day
this large study comprised 4,449 relatively young type 2 diabetic patients ( mean age 57.7  years , range 2875 ) with an average duration of diabetes of 6.1  years . at baseline
they had moderately controlled median bp ( 140/84  mmhg ) , but attenuated lowering of night - time sbp ( 6.8% ) .
the median hba1c was relatively low ( 7.3% ) , but the cardiovascular risk factor profile was high ( 67.0% had 4 cardiovascular risk factors ) . as evaluated by spearman correlation coefficient analysis ,
the factors most strongly correlated with the variation in albuminuria within the normoalbuminuric range comprised bp variables , most strongly , night - time sbp and further bp indices : mean 24  h sbp , night - time sbp , office sbp in men ( but not in women ) , mean 24  h dbp and office dbp as well as pulse pressure as an index of vascular stiffness .
the bp data are in good agreement with previous reports in smaller cohorts reported in the literature . in type 1 diabetes ,
higher night - time sbp predicted the onset of microalbuminuria   and the occurrence of cardiovascular events , respectively .
similarly in type 2 diabetes , attenuated dipping and elevated night - time bp are frequent .
night - time sbp was higher than daytime sbp in adult diabetic patients who developed microalbuminuria .
attenuated dipping was also found to be correlated with coronary events . in one relatively small recent study , however , the correlation of albuminuria to night - time bp dipping was less tight than to absolute bp .
the abpm sub - cohort with higher night - time than daytime bp had significantly higher ( p  =  0.0076 by wilcoxon rank sum test ) albumin excretion compared with patients with lower night - time than daytime bp . in a very small sample of patients with type 2 diabetes , a recent report found that pulse pressure ( as a potential indicator of vascular stiffness ) was related to albumin excretion .
the present study , in normoalbuminuric type 2 diabetic patients , extends the findings on pulse pressure in the large cross - sectional study in microalbuminuric and proteinuric type 2 diabetic patients by tanaka et al . :
the present study documents that a relationship between pulse pressure and albuminuria is found even in normoalbuminuric type 2 diabetic patients .
tanaka et al . had also noted a correlation with aortic pulse wave velocity and carotid intima  media thickness . in a small sample of normo- and microalbuminuric type 2
diabetic patients , albuminuria was correlated with markers of endothelial cell dysfunction , and this may explain , at least in part , this correlation to pulse wave velocity . in the present study albuminuria was also significantly correlated with indices of glycaemic control , i.e. hba1c , fasting glucose and duration of diabetes , as well as insulin treatment as a categorical variable .
individuals requiring insulin treatment and individuals with longer duration of diabetes presumably have more advanced renal lesions .
furthermore , bmi and the categorical variables of elevated waist circumference and the metabolic syndrome according to ncep - atp - iii criteria   were correlated with albuminuria as well .
this observation is again in line with previous communications and the observation that uae reflects insulin resistance . in the general non - diabetic population   and in essential
even sub - diabetic glycaemia increased the risk of microalbuminuria in the  framingham offspring study . in the ukpds study , the patients who presented with type 2 diabetes and had lower glycaemia had also a lower risk of albuminuria . in the australian diabetes , obesity and lifestyle study ,
it is particularly postprandial glycaemia , not measured in the present study , which is best correlated with albuminuria , so that the overall impact of glycaemia may even have been somewhat underestimated in the present study . in the general population
the metabolic syndrome is associated with both microalbuminuria and chronic kidney disease   and the same is observed in hypertensive patients . in the general non - diabetic population , waist circumference ,
an index of visceral obesity , also predicted higher albumin excretion . in type 1   and type 2 diabetes as well , waist circumference had been found to be a predictor of microalbuminuria . in the above
study a positive relationship was found between albuminuria and estimated gfr , indicating that hyperfiltration presumably plays a role in the pathogenesis of high normal albuminuria in type 2 diabetes .
a note of caution is appropriate , however , since in diabetic patients egfr is not a reliable indicator of true gfr , at least in individual patients . in agreement with reports in the literature on patients with type 1   and type 2 diabetes , albuminuria
was also correlated , although not markedly , to triacylglycerol , total cholesterol and ldl - cholesterol . a recent report found a positive correlation between uric acid and albuminuria in male type 2 diabetic patients   in whom confounding factors had been excluded , such as use of allopurinol , diuretics or alcohol consumption . in the present roadmap study the correlation was negative and this persisted even when adjusted for the potential confounding effect of alcohol use .
the use of and presumably need for antihypertensive medication , particularly amlodipine , was positively related to albuminuria .
the correlation with antihypertensive medication may be an example of confounding by indication , i.e. that patients with more severe and more advanced disease required antihypertensive medication and had also higher rates of albuminuria .
the significant effect of amlodipine , however , may be more complex . at the time of screening
the patients had not yet received , or were off , renin  angiotensin receptor blockers for at least 6  months .
the strength of our study is that we analysed uacr in a large sample of type 2 diabetic patients without kidney disease ( no microalbuminuria , egfr  >  60  ml  min 1.73  m ) . as the inclusion and exclusion criteria
were fulfilled by the majority of the screened patients , this study population is representative of the majority of type 2 diabetic patients . moreover , our data on uacr are based on the measurement of albuminuria in three morning spot urines . it should be noted that only 10% of the total variance of the uacr could be explained by the degree of blood glucose control , bp variables , lipids and age .
analysed the correlation of albumin excretion ( uae ) with cardiovascular risk factors in 7,841 patients of the prevend cohort . in their cohort ,
taken from the general population , only 3.5% had diabetes and 14% microalbuminuria at baseline .
they found a correlation between uae and male sex , age , sbp , dbp , fasting glucose levels , bmi , smoking and creatinine clearance . in a multivariate analysis only 22% of the variance of uae
since all patients in the roadmap study had diabetes , this observation might explain why we were only able to explain 10% of the variance of the loge uacr .
the relatively modest correlation may also be because of the fact that most of the patients were in the low normoalbuminuric range at baseline . in this low range
the intra - individual variability of the three repeated uacr measurements was 55% in the roadmap cohort .
therefore , the correlation observed points more to the direction ( thus providing a potential target of treatment ) rather than reflecting the magnitude of the relationship .
the identified variables correlate not only with the degree of albuminuria within the normoalbuminuric range but might also be predictors for the development of microalbuminuria ( table  8) . 

table  8determinants of baseline values for the development of microalbuminuriavaluestudydirect hope benedict agen.d.+n.d.male sex++n.d.sbpn.d.+=dbpn.d.==pulse pressuren.d.n.d.=bmi kg / mn.d.+n.d.cholesteroln.d.=n.d.low hdl - cholesteroln.d.=n.d.smokingn.d.+n.d.baseline uae+n.d.n.d.retinopathy+n.d.n.d.hba1c+n.d.n.d.n.d .
, not determined ; + , positive correlation ; = , no significant correlationthe diabetes incidence after renal transplantation ( direct ) study : 3,326 and with type 1 and 1,905 type 2 diabetes were followed for 4.7  yearsthe heart outcomes prevention evaluation ( hope ) study : 9,043 patients with and without type 2 diabetes were followed for 4.5  years and determinants of albuminuria assessedthe bergamo nephrologic diabetes complications trial ( benedict ) : 1,204 patients with type 2 diabetes were followed for 3.6  years and risk factors for the development of microalbuminuria analysed determinants of baseline values for the development of microalbuminuria n.d . , not determined ; + , positive correlation ; = , no significant correlation the diabetes incidence after renal transplantation ( direct ) study : 3,326 and with type 1 and 1,905 type 2 diabetes were followed for 4.7  years the heart outcomes prevention evaluation ( hope ) study : 9,043 patients with and without type 2 diabetes were followed for 4.5  years and determinants of albuminuria assessed the bergamo nephrologic diabetes complications trial ( benedict ) : 1,204 patients with type 2 diabetes were followed for 3.6  years and risk factors for the development of microalbuminuria analysed studies in normoalbuminuric diabetic patients have additional limitations .
first , on the one hand in diabetic patients albuminuria is certainly correlated with the severity of glomerular lesions , but the correlation is not strict , particularly in type 2 diabetes .
on the other hand , diabetic glomerular lesions may even precede the onset of albuminuria .
second , microalbuminuria is present in 16% of patients at the time of diagnosis of type 2 diabetes .
microalbuminuria frequently precedes the onset of overt type 2 diabetes   and one potential explanation may be the relatively strong correlation between albuminuria and the metabolic syndrome , a prediabetic state with insulin resistance . in conclusion , the present baseline data of the roadmap study suggest that albuminuria is a continuous variable , and that even in normoalbuminuric type 2 diabetic patients albumin excretion rates are correlated with a number of factors which are potentially susceptible to therapeutic intervention , although certainly correlation does not necessarily imply causality .
 aims / hypothesisin contrast to microalbuminuric type 2 diabetic patients , the factors correlated with urinary albumin excretion are less well known in normoalbuminuric patients . 
 this may be important because even within the normoalbuminuric range , higher rates of albuminuria are known to be associated with higher renal and cardiovascular risk.methodsat the time of screening for the randomised olmesartan and diabetes microalbuminuria prevention ( roadmap ) study , the urinary albumin / creatinine ratio ( uacr ) was 0.44  mg / mmol in 4,449 type 2 diabetic patients . 
 the independent correlates of uacr were analysed.resultsindependent correlates of uacr during baseline were ( in descending order ) : night - time systolic bp ( rs  =  0.19 ) ; hba1c ( rs  =  0.18 ) ; mean 24  h systolic bp ( rs  =  0.16 ) ; fasting blood glucose ( rs  =  0.16 ) ; night - time diastolic bp ( rs  =  0.12 ) ; office systolic bp , sitting ( rs  =  0.11 ) , standing ( rs  =  0.10 ) ; estimated gfr ( rs  =  0.10 ) ; heart rate , sitting ( rs  =  0.10 ) ; haemoglobin ( rs  =  0.10 ) ; triacylglycerol ( rs  =  0.09 ) ; and uric acid ( rs  =  0.08 ; all p    0.001 ) . 
 significantly higher albumin excretion rates were found for the following categorical variables : higher waist circumference ( more marked in men ) ; presence of the metabolic syndrome ; smoking ( difference more marked in males ) ; female sex ; antihypertensive treatment ; use of amlodipine ; insulin treatment ; family history of diabetes ; and family history of cardiovascular disease ( more marked in women).conclusions / interpretationalthough observational correlations do not prove causality , in normoalbuminuric type 2 diabetic patients the albumin excretion rate is correlated with many factors that are potentially susceptible to intervention.trial registration : clinicaltrials.gov i d no . : 
 nct00185159funding : this study was sponsored by daichii - sankyo . 
Trial registration:
Funding:
Introduction
Methods
Results
Discussion