© Freund Publishing House Ltd.

, London Journal of Pediatric Endocrinology & Metabolism, 23, xxx-xxx (2010)

Risk Factors for Early Onset of Diabetic Nephropathy

in Pediatric Type 1 Diabetes
Patrícia Paz Cabral de Almeida Salgado1; Ivani Novato Silva2, Érica Cristina Vieira3;
and Ana Cristina Simões e Silva4
1
Post-Graduate Student, Medical School, 2Associate Professor of the Department of Pediatrics,
3
Undergraduate Student, Medical School, 4Associate Professor of the Department of Pediatrics –
all of Federal University of Minas Gerais (UFMG), Brazil

ABSTRACT considering the most severe forms. Clinical

Aim: Diabetic nephropathy (DN) is a frequent
complication in patients with long-standing
type 1 diabetes mellitus (DM1). The objective
of this study was to assess the prevalence of
DN in DM1 patients diagnosed during
childhood and its association with clinical and
metabolic variables, such as age at diagnosis of
DM1, glucose control, dyslipidemia, hyper-
tension and the occurrence of diabetic retino-
pathy (DR). Methods: The medical records of
205 patients admitted to the Pediatric
Endocrinology Division at the Hospital das
Clínicas da Universidade Federal de Minas
Gerais, in Belo Horizonte, Brazil, were
analyzed. For the analysis of survival and
prognostic factors, the Kaplan-Meyer method
and the COX regression model were used.
Results: The mean disease duration was 11.32
± 4.02 years and the mean age at diagnosis was
6.10 ± 3.54 years. Microalbuminuria was
present in 11.2% of them, proteinuria in 6.8%
and end-stage renal disease (ESRD) in 2.9%.
There was a significant association between
the occurrence of microalbuminuria or pro-
teinuria and poor glucose control (p=0.025 and
p=0.005, respectively), higher LDL cholesterol
levels (p=0.006 and p=0.004, respectively) and
age greater than 6 years at diagnosis (p=0.049
and p=0.05, respectively). Proteinuria was also
associated to the occurrence of DR (p=0.016).
Conclusion: Our data showed that the
prevalence of DN was higher than expected in
this young population studied, especially
Corresponding author:
Ivani Novato Silva, MD, PhD
ivanins@medicina.ufmg.br
VOLUME 23, NO. 9, 2010
and laboratory factors associated to ND were:
poor long-term glucose control, higher levels of
LDL-C, higher age at diagnosis and the
occurrence of DR.
KEY WORDS
diabetes mellitus type 1, proteinuria, blood
glucose, chronic renal insufficiency, end-stage
renal disease
INTRODUCTION
Diabetic nephropathy (DN) is one of the most
frequent chronic complications of type 1 diabetes
mellitus (DM1), leading to high morbidity and
mortality rates. After 20 years suffering from
DM1, about 20% of these patients develop DN,
which is the major cause of mortality and also
increases medical, economical and social costs 1.
Since the 1980s, microalbuminuria is
considered the earliest marker for DN and the
assessment of urine albumin excretion is still the
best non-invasive method for detecting DN2,3. In
addition, about 30 to 45% of patients with micro-
albuminuria will progress to macroalbuminuria
within an average period of 10 years4-6.
Although the pathophysiology of DN is not
fully understood, high blood glucose has a key
role in its occurrence7. In addition to high blood
glucose levels, increased blood pressure,
smoking, dyslipidemia and retinopathy have been
associated to the development and progression of
DN8-11. DN is also associated to high frequency
of death due to cardiovascular causes. Patients
with diabetes and proteinuria have a relative risk
for premature death much higher than the diabetic
1
2 P.P.C. DE ALMEIDA SALGADO ET AL
population free from nephropathy12.
Few studies have evaluated risk factors for
DN in childhood onset DM113,14. In northern
Sweden, Svensson et al.13 observed that
inadequate glycemic control, also during the first
5 years of diabetes, seems to accelerate time to
occurrence of DN, whereas a young age at onset
of diabetes seems to prolong the time to develop-
ment of microvascular complications. On the
other hand, the Oxford Prospective Regional
Study group reported that prepubertal duration of
diabetes and prepubertal hyperglycemia contri-
bute to the risk of postpubertal micro-
albuminuria14. More recently, the Oxford
Prospective Regional Study group15 concluded
that, in childhood onset DM1, the only modifiable
predictors were poor glycemic control for the
development of microalbuminuria and poor
control and microalbuminuria (both persistent and
intermittent) for progression to macroalbumin-
uria. Indeed, the analysis of other pediatric DM1
series may help understanding the natural history
of DN. Therefore, the aim of this study was to
assess the prevalence and risk factors associated
to the development of DN in childhood onset
DM1 Brazilian population.
PATIENTS AND METHODS
In this retrospective cohort study, data from
all patients with DM1 diagnosed before 1999 and
admitted to the Pediatric Endocrinology Division
at the Hospital das Clínicas da Universidade
Federal de Minas Gerais (HC-UFMG), in Belo
Horizonte, Brazil were analyzed (January 1999 to
December 2005). Of the 228 patients initially
enrolled, three were excluded for having Wolfram
syndrome and Systemic Lupus Erythematosus
and 19 for not having enough clinical and
laboratory assessment for the analysis. DM1
patients with other diseases, renal or not, that
could produce by themselves microalbuminuria
or proteinuria and/or blood pressure elevation
were automatically excluded from the study.
Methods
The Ethics Committee of the Federal
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
University of Minas Gerais approved the study.
The diabetic patients from the Pediatric
Endocrinology Division followed a protocol
determining 3-month interval clinical and
laboratorial evaluations. Data obtained from the
beginning of the patient’s follow-up at the HC-
UFMG were retrieved from the medical charts.
All laboratorial measurements were performed
according to standard protocols of the Institution.
Assessment of diabetic nephropathy
The standard classification for diabetic
nephropathy includes the following categories:
hyperfiltration, microalbuminuria, overt protein-
uria and end stage renal disease (ESRD).
However, due to the well known limitations in
estimating glomerular filtration rate, we opt to
sort our patients into four groups: patients without
microalbuminuria, patients with microalbumin-
uria, patients with overt proteinuria and patients
at ESRD according to results of microalbumin-
uria or proteinuria in 24-hour urine and the need
for renal replacement therapy. Microalbuminuria
was diagnosed in patients with at least two results
of urinary excretion of albumin between 20 and
199µg/min in a 12-month period (chemolumi-
nescence); and overt proteinuria in those with
albumin excretion greater or equal to 200 µg/min
(dry chemistry), according to the American
Diabetes Association (ADA) and the DCCT
criteria4,7. Patients who required renal replace-
ment therapy (dialysis or transplantation) due to
the progression of DN were included in the ESRD
group. These patients were rigorously evaluated in
order to exclude other associated renal diseases.
Assessment of hypertension
Data of blood pressure (BP) were evaluated in
the last assessment for patients without micro-
albuminuria, and at the moment micro-
albuminuria or overt proteinuria and ESRD were
detected. According to the Fourth Report of the
Task Force16 systolic and/or diastolic pressure
persistently above the 95th percentile for sex, age
and height percentile, when detected on at least
three different occasions in a one-year period
were used for diagnosing hypertension.
 RISK FACTORS FOR DIABETIC NEPHROPATHY
Assessment of blood glucose control
All results of glycated hemoglobin measured
from the admission of the patient at HC-UFMG
were assessed to determine the mean hemoglobin
A1c (HbA1c) of each patient until the outcome –
microalbuminuria and proteinuria.
Assessment of lipid profile
The mean plasmatic values of total cholesterol
(TC), low-density cholesterol lipoprotein ( LDL-
C) and triglycerides (measured by dry chemistry)
were calculated until the outcome: micro-
albuminuria and proteinuria.
Assessment of diabetic retinopathy (DR)
The results of all ophthalmologic assessments
performed since patient’s entry at the HC-UFMG
were studied. If changes were found during
binocular indirect ophthalmoscopy after dilating
the pupils, the investigation progressed according
to the ADA recommendations4. The results were
classified as no DR, nonproliferative DR and
proliferative DR, according to the criteria of the
Early Treatment Diabetic Retinopathy Study17.
Statistical Analysis
All analyses were done with the SPSS
statistical software and the level of significance
was set as p<0.05.
For the analysis of survival and prognostic
factors, the Kaplan-Meyer method and the COX
regression model were used. To identify the
associations with adverse outcomes (micro-
albuminuria, proteinuria and ESRD), the
continuous variables were dichotomized in cutoff
points as recommended by the literature4:
TC<170, LDL <100, triglycerides <100. HbA1c
was tested at different cutoff points: 7, 8, 9, 10
and 11 in order to identify the point of the
greatest power to discriminate the groups. The
best cutoff point identified after analysis was 10.
The variable “age at diagnosis” was also tested at
the cutoff point 6 (median), 7, 8, 9 and 10 years
and the best discriminative value for this variable
was 6 years. Therefore, both variables were
VOLUME 23, NO. 9, 2010
3
dichotomized at these best discriminative points
identified after analysis. The other variables were
sex and hypertension. Relative risk (RR) and the
confidence interval (IC) were quantified using the
COX proportional risk model.
The analysis was conducted in two steps. In
the first step, univariate analysis was performed
by Kaplan Meyer survival method. Then, a
logistic regression model was applied to identify
variables that were independently associated with
DN. Only those variables that were found to
present p ≤ 0, 25 in log-rank test in univariate
analysis were included in the regression model.
Next, using a backward elimination strategy,
those variables that retained a significant
independent association (p<0.05) were included
in the final models.
All patients were included in the survival
analysis. For patients with proteinuria, the time
until the detection of microalbuminuria was taken
into account. Patients with ESRD were included
only in the calculation of DN prevalence, but
were excluded from the univariate analysis by the
Kaplan-Meyer method and of the COX regression
model because of small number of events.
For the association between diabetic
retinopathy and nephropathy, univariate analysis
using chi-square with the Yates correction and the
Fischer´s exact test, when indicated, was used.
For this comparison, the patient current status was
considered. Thus, patients with proteinuria were
excluded when microalbuminuria was assessed.
RESULTS
Two hundred and five patients, 105 males
(51.2%), aged 17.4 ± 4.12 years (7.6 to 27.4) at
the last visit were included. Mean age at
diagnosis of diabetes was 6.1 ± 3.54 years (0.8 to
15.5). The average disease duration determined at
the last visit of each patient was 11.32 ± 4.02
years (3.0 to 22.8), with only six patients (2.9%)
with less than five years of diabetes at that time.
The mean follow-up time was 9.8 ± 4.03 years,
with the shortest time of one year and longest of
20.1 years.
The mean plasma HbA1c values during the
follow-up were 9.4 ± 1.43% (average of 2
4 P.P.C. DE ALMEIDA SALGADO ET AL

measurements/patient/year). The mean plasma
levels of TC were 175 ± 38.3 mg/dL, LDL-C,
104.8 ± 31.2 mg/dL, and triglycerides, 81.9 ±
47.3 mg/dL. There were no patients receiving
lipid lowering treatments.
Blood pressure of 156 (76.1%) patients was in
the normal range and it was elevated in 49
(23.9%) of them.
The assessment of urinary albumin excretion
at the last visit showed that 162 patients (79%)
had urinary albumin excretion within normal
limits, 23 (11.2%) had microalbuminuria, 14
(6.8%) proteinuria and 6 (2.9%) ESRD. All the
six ESRD patients were on dialysis program.
Among the patients with microalbuminuria, 22
(95.7%) were taking angiotensin converting
enzyme (ACE) inhibitors or angiotensin II
receptor antagonists (ARA); and among those
with proteinuria, 12 (85.7%) were taking those
drugs at the same time of the proteinuria was
detected.
Table 1 shows the mean values of clinical and
laboratory variables in the different groups at the
time of the last assessment.
Factors associated with progression to
microalbuminuria
Table 2 shows the RR, 95% CI and p values of
comparisons between the variables studied and
progression to microalbuminuria in diabetic
patients. It was detected that mean LDL-C>100,
HbA1c ≥10 and age greater than 6 years at
diagnosis were associated with progression to
microalbuminuria

TABLE 1
Clinical characteristics and laboratorial measurements of 205 DM1 children and adolescents at the last visit
Variables Normal albumin Microalbuminuria Proteinuria ESRD
excretion (n=162) (n=23) (n=14) (n=6)
Female 82(50.6%) 7(30.4%) 7(50%) 4(66.7%)
Male 80(49.4%) 16(69.6%) 7(50%) 2(33.3%)
Age at diagnosis of DM1 6.0 ± 3.6 6.3 ± 3.5 6.2 ± 3.0 7.4 ± 4.3
(years)
Disease duration (years) 10.8 ±4.0 12.6 ± 3.6 14.0 ± 4.1 15.0 ± 3.3
Age at diagnosis of the event - 15.5 ± 3.28 17.8 ± 3.36 20.2 ± 3.95
of interest (years)
High BP 27 (16.7%) 6 (26.1%) 10 (71.4%) 6 (100%)
HbA1c (%) 9.3 ± 1.4 9.3 ± 1.5 10.8 ± 1.4 9.4 ± 1.1
Total cholesterol (mg/dl) 170.4 ± 35.3 170.5 ± 32.7 197.8 ± 27.5 262.4 ± 39.8
LDL cholesterol (mg/dl) 101.3 ± 28.4 100.5 ± 25.6 121.6 ± 23.7 176.5 ± 44.9
Triglycerides (mg/dl) 77.6 ± 43.9 76.2 ± 44.6 116.9 ± 62.1 136.6 ± 48.1

TABLE 2
Relative risk and confidence interval of progression to microalbuminuria in 205 DM1 children and adolescents
Event Censured Coefficient Standard Relative 95% CI p
error risk
Sex
Male 24 80 0.31 0.34 1.36 0.70 a 2.63 0.36
Female 14 82
Mean LDL-C (mg/dl)
>100 22 48 1.05 0.33 2.86 1.50 a 5.45 0.001
≤ 100 16 114
HbA1c (%)
≥ 10 21 49 0.97 0.33 2.64 1.39 a 5.01 0.003
<10 17 113
Age at diagnosis (years)
>6 20 76 0.84 0.34 2.32 1.20 a 4.47 0.012
≤6 18 86

JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM

 RISK FACTORS FOR DIABETIC NEPHROPATHY 5

TABLE 3
Relative risk and confidence interval of progression to proteinuria in 205 DM1 children and adolescents
Event Censured Coefficient Standard Relative 95% CI p
error risk
Sex
Male 8 80 -0.27 0.49 0.76 0.29 a 1.98 0,58
Female 9 82
Mean LDL-C (mg/dl)
>100 14 48 2.62 0.76 13.76 3.13 a 60.6 0,001
≤ 100 3 114
HbA1c (%)
≥ 10 15 49 2.60 0.75 13.45 3.08 a 58.8 0,001
<10 2 113
Age at diagnosis (years)
>6 10 76 1.37 0.52 3.93 1.43 a 10.8 0,008
≤6 7 86

TABLE 4
Association between diabetic retinopathy and nephropathy in 205 DM1 children and adolescents
Retinopathy Normoalbuminuria Microalbuminuria Proteinuria
Absent 127/137 (92.7%) 18/21 (85.7%) 8/12 (66.7%)
Nonproliferative 9/137 (6.6%) 3/21 (14.3%) 0
Proliferative 1/137 (0.7%) 0 4/12 (33.3%)
Not assessed 25 2 2
p value* p=0.38 p=0.016
* Chi-square test

In the multivariate analysis, the initial model
included the variables HbA1c with cutoff point of
10, mean LDL and age at diagnosis, and all of
them remaining statistically significant (p=0.025,
p=0.006 and p=0.049, respectively). Survival
curve for microalbuminuria according to HbA1c
Not is shown in Figure 1.
on
file
Factors associated with progression to proteinuria
Table 3 shows the RR, 95% CI and p values of
the comparison between the variables studied and
progression to proteinuria in diabetic patients.
Note that all variables, except for sex and
hypertension, are associated with progression to
proteinuria: mean TC, mean LDL-C, mean
triglycerides, HbA1c at the 9, 10 and 11 cutoff
points, age at diagnosis.
In the initial model of the multivariate analysis
the levels of HbA1c with cutoff point of 10,
LDL-C, triglycerides and mean TC as well as age
at diagnosis were included. Using a backward
elimination strategy, three variables remained
with statistical significance: age (p=0.05), LDL-C
(p=0.004) and HbA1c (p=0.005). The survival
curves stratified according HbA1c and mean
LDL-C are displayed in Figures 2 and 3.
Association between diabetic retinopathy and DN
Twenty-one patients showed retinal changes,
comprising 12% of the group studied (n=176): 12
(6.9%) had nonproliferative retinopathy, and 9
(5.1%) had proliferative retinopathy. The group
of patients with microalbuminuria had changes in
ophthalmologic assessment in 14.3% of cases. It
occurred in 33.3% of patients with proteinuria
and 80% of those with ESRD. Normoalbuminuric
patients had DR in 7.3% (Table 4). There was an
association between proteinuria and retinal
changes (p = 0.016). There was no association
between microalbuminuria and DR (p = 0.38).
DISCUSSION
The emergence of DN after 20 years of
disease in about 20% of patients with DM1 is

VOLUME 23, NO. 9, 2010

6 P.P.C. DE ALMEIDA SALGADO ET AL
well described in several populations18,19. The
incipient identification of renal disease by means
of measurement of microalbuminuria in the
pediatric age range13,14, on the other hand, is not
well determined yet. There are not many reports
of data obtained from young populations. In the
present study we assessed the occurrence of DN
in diabetic patients diagnosed during childhood
and with duration of 11.3 years of diabetes. Most
reports on DN include patients with longer lasting
disease and later age at diagnosis18,19.
The prevalence of DN found in the present
study was 21%; in that, 9.8% of patients had
proteinuria and ESRD. It can be observed that as
patient age increased, the more severe events
occurred, corroborating the well-known relation
between the onset of chronic complications and
the duration of disease. What is striking,
however, is that severe complications occurred at
a relatively early age.
Some investigations involving children and
adolescents with the mean duration of DM1
similar to that of this study revealed a 4 to 21%
prevalence of microalbuminuria, proteinuria and
ESRD being rare20,21. Comparing our findings
with the literature, one suspects the occurrence of
a higher frequency of more severe forms of renal
involvement. In another Brazilian study22 a high
prevalence of DN was also found, similar to what
was observed in the present study. In the
population studied here, the highest levels of
HbA1c were associated with the development of
microalbuminuria and proteinuria. Inadequate
glucose control is considered the main modifiable
risk factor for DN in patients with DM113,14,18-21.
The Diabetes Control and Complication Trial
(DCCT)7 and the follow-up study Epidemiology
of Diabetes Interventions and Complications
(EDIC)23 clearly demonstrated that intensive
glucose control delays or even prevents the
appearance and progression of DN. The high
frequency of DN in our study might be explained,
thus, by inappropriate glucose control. However,
this is not a consensus finding in the pediatric age
range. Other studies showed the occurrence of
DN in patients with better glucose control13,24. In
addition, studies with adult population detected
small differences in HbA1c levels related to the
occurrence of DN: average values of 7.3% in
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
patients without DN and 8.4% in those with
microalbuminuria or proteinuria18,19. Another fact
that should be taken into consideration is that
some data suggest that oscillating glucose can
have more deleterious effects than constant high
glucose on endothelial function and oxidative
stress, which is a key player in the development
of diabetes complications. Many reports have
already shown that an acute increase of glycemia
induces endothelial dysfunction in both normal
and diabetic subjects25. On the other hand, it was
observed that glucose control seemed not to be
the only determining factor in the development of
DN. The literature strongly suggests that DN
occurs more frequently in certain families,
demonstrating the inherited predisposition for this
complication of DM26. Therefore, despite long-
term glucose control in the patients in our study
being far from ideal, one cannot disregard other
causative factors for the higher frequency of DN
found.
There are several studies relating changes in
lipid profile to diabetic nephropathy9,27,28. But
there are issues concerning the causality of
dyslipidemia in pediatric patients with DM1. The
association between dyslipidemia and the risk of
developing microalbuminuria as well as
association between increased levels of LDL-C
and progression of DN was reported9,27. Glucose
control and positive family history for dys-
lipidemia are also important determinants of lipid
levels in children27. Both factors may contribute
to the occurrence of microalbuminuria and the
subsequent risk of cardiovascular disease. The
association found between higher levels of LDL-
C and microalbuminuria or proteinuria in our
DM1 population corroborates the literature. There
are evidences of the association between
advanced glycation end products (AGE) and
increased serum cholesterol, implicating the
involvement of lipids in the formation of AGE
and, consequently, in DN29. Indeed, these
children present a sum of risk factors for
complications, considering, also, the reports
showing that fat striae in the aorta could be
already found at the age of three years, in
children presenting dyslipidemias30.
Hypertension, conversely, was not associated,
in the present study, with progression to DN. The
 RISK FACTORS FOR DIABETIC NEPHROPATHY
explanation for this finding may be the use of ACE
inhibitors or ARA, immediately after the detection
of microalbuminuria, that might have prevent the
occurrence of hypertension in those patients.
Several studies demonstrated that children
with DM1 presenting in earlier age have a lower
risk of developing DN14,28,31. In fact, in the
present study an association between older age at
diagnosis and occurrence of microalbuminuria
and proteinuria was also found. In a recent study,
children diagnosed prior to five years of age had a
higher microalbuminuria-free interval, when
compared to those diagnosed between 5 and 11
years, and after 11 years31. In addition, after 10
years of diabetes, these children also had low
cumulative prevalence of microalbuminuria com-
pared to the other two age groups. This does not
mean that poor metabolic control in pre-pubertal
children is not related to higher risk of DN, since
there is evidence, as the Oxford Prospective
Regional Study group reported, that pre-pubertal
hyperglycemia contributes to the risk of
postpubertal microalbuminuria14.
The association between DR and DN in DM1
patients is described in the literature1. In the
present study, an increasing proportion of DR was
found related to the worsening of renal damage,
which suggests an already significant systemic
damage even in a young population such as the
one studied. It has been suggested that DN and
DR are specific manifestations of the generalized
endothelial dysfunction of diabetes. This would
also be a possible explanation for the existing
association between increased albumin excretion
and atherosclerotic disease in diabetic patients32.
Prospective studies showed that when the
diagnosis of retinal damage is made, there is an
increased risk for the emergence of DN33, as there
is also a higher risk for DR in patients with
microalbuminuria34.
Other clinical factors have been associated
with the occurrence of DN. In previous reports,
male sex, smoking, and low birth weight have
emerged as risk factors for the development of
nephropathy in young adults with type 1 dia-
betes8-11. Black race, low socioeconomic status
and the amount and source of protein and fat in
the diet have also been related to DN35.
Concerning gender differences, we did not find
VOLUME 23, NO. 9, 2010
7
an association between male sex and nephropathy
in our study. A possible explanation for the
absence of difference is the limited number of
patients in each category of DN. Although
microalbuminuria was more frequently detected
in male patients than in females (69.6% vs.
30.4%, Table 1), significant differences between
genders were not found when the whole group of
patients was analyzed. It should be pointed out
that, despite the information of race in the
medical records of our patients, we opt not to
include this variable in the analysis since ethnical
definition on clinical basis is quite impossible in
Brazilian populations due to intense misce-
genation as previously reported36. Due to the
retrospective design of our study, we were not
able to evaluate precisely the frequency of
smoking habit and previous low birth weight
among our patients and the records relating to
socioeconomic status and the diet of our
population were not complete enough to allow a
precise definition of these factors. These variables
might contribute to the high frequency of DN in
our series. Therefore, prospective cohort studies
including larger samples of pediatric type 1
diabetes patients are necessary in order to fully
evaluate risk factors for nephropathy.
In conclusion, the prevalence of DN was
higher than expected in our young DM1
population, especially considering the most
severe forms. The factors associated with the
development of DN detected were inadequate
long-term blood glucose control, high LDL-C
levels, older age at diagnosis and presence of DR,
in accordance to what has been described in long
duration DM. Improving long term glucose
control and maintaining appropriate lipid profile
seems to be fundamental in the attempt of
reducing DN in young people. In addition, the
presence of DR in these patients must be an alert
for the possibility of associated renal damage.
Our findings point to improving the therapeutic
goals to be defined and must be taken into
account when creating new protocols for
management of diabetic children and adolescents.
ACKNOWLEDGMENTS
The research was partially supported by
8 P.P.C. DE ALMEIDA SALGADO ET AL
CAPES (Brazilian coordination of academic
funds)
There is no potential conflict of interest
relevant to this article.
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Figure legends

Fig. 1: Survival curve for microalbuminuria stratified according to glycated hemoglobin (HbA1c) levels

Fig. 2: Survival curve for proteinuria stratified according to glycated hemoglobin (HbA1c) levels

Fig. 3: Survival curve for proteinuria stratified according to mean LDL-C levels

VOLUME 23, NO. 9, 2010