Duration of type 2 diabetes is an indicator
for occurrence of nephropathy
Ching-Heng Lin1, Wu-Chang Yang2, Pesus Chou1
1. Community Medicine Research Center & Institute of Public Health, National
Yang-Ming University, Taipei, Taiwan, R.O.C.
2. Division of Nephrology, Department of Medicine, School of Medicine, Taipei
Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan,
R.O.C.
Summary
Introduction
Diabetic nephropathy is the major cause of end-stage renal disease (ESRD) and
40% of type 2 diabetes will progress to diabetic nephropathy. In order to prevent of
ESRD, a diabetic nephropathy screening and the appropriate intervention were
recommended. The purpose of this study was to determine the prevalence of diabetic
nephropathy and to define associated factors among type 2 diabetes mellitus. Finally,
we assessed the association between the duration of type 2 diabetes and diabetic
nephropathy.
Methods
During 1991-93, a community-based survey of type 2 diabetes for inhabitants aged
30 and over in Kinmen was conducted. A total of 971 type 2 diabetes was ascertained.
In 1999, we carried out a screening for diabetic nephropathy . 577(59.4%) out of type
2 diabetes were examined. Diabetic nephropathy was defined as a random urinary
protein-to-creatinine ratio (UPCR) (ratio≧0.2) that had been indicate to a tool of
screening for nephropathy. The duration of diabetes was classified into four categories:
<10 years, 10-12 years, 13-15 years, and ≧16 years.
Results
One hundred and seventy-five of 577 of diabetes were diagnosed with diabetic
nephropathy, and the prevalence was 30.3 %. Based on multiple logistic regression
analysis, the significant associated factors for diabetic nephropathy were systolic
blood pressure, duration of diabetes, BUN, and HbA1c.Odds ratios for duration were
estimated as 1.53 (95%CI: 0.51-4.56) in 10-12 years, 9.50 (95%CI: 1.13-80.18) in
13-15 years, and 11.12(95%CI: 1.29-96.12) in ≧16 years compared with <10 years.
Conclusions
This community-based screening for diabetic nephropathy displayed systolic blood
pressure, duration of diabetes, BUN, and HbA1c were the most important associated
factors. Duration of diabetes is an indicator for occurrence of nephropathy. The risk of
occurrence of nephropathy would increase rapidly when the duration of diabetes was
over 12 years.
Introduction
The microvascular complications that are specific to diabetes include retinopathy,
nephropathy, and neuropathy. According to the reports of the U.S. Renal Data System,
there has been a continual increase in the incidence of end-stage renal disease (ESRD)
among patients with diabetes, for the most part of those with type 2 diabetes1.
Diabetic nephropathy is the major cause of end-stage renal disease (ESRD) 2. The
incidence of ESRD was the 20 times in Pima Indians who have the world’s highest
incidence of type 2 diabetes compared with the incidence of ESRD in general U.S.
population3.
In histology, about 40% of type 2 diabetes will progressed to diabetic nephropathy4.
In order to prevent of ESRD, a diabetic nephropathy screening and the appropriate
intervention were recommended. The aims of this study were to determine the
prevalence of diabetic nephropathy and to define associated factors among type 2
diabetes mellitus. Finally, we assessed the association between the duration of type 2
diabetes and diabetic nephropathy.
Methods
1. Organization of community-based screening for nephropathy
We conducted a community-based survey for type 2 diabetics targeted to subjects
aged 30 years or more in Kinmen, Taiwan, between January, 1991 and December,
1993. Another screening program for early detection of nephropathy among type 2
diabetics found in the above screening was conducted in 1999. Figure 1 shows the
procedures of mass screening for type diabetes between 1991-1993 and nephropathy
screening in 1999.
The reason of initiating screening program for nephropathy after six years of
mass screening is due to the fact that since Kinmen is an offshore island from Taiwan
and lacking of medical resources, screening for nephropathy involved a lot of
difficulties, including mobilization of manpower and facility to Kinmen, coordination
between clinical personnel and field work, and transportation between Taiwan and
Kinmen. Eventually, an organized team for screening nephropathy had been
successfully organized in 1999.
2. Subjects and Study design
The target population consisted of 1,123 asymptomatic type 2 diabetics that met
1999 WHO criteria5. Of 1,123 subjects, there were 152 subjects who emigrated or
died between 1994 and 1998. After excluding these subjects, the remaining 971 type 2
diabetics had the uptake of slip-lamp and fundus check-up annually. Table 1 shows
age and sex distributions of this cohort. These 971 participants were invited to receive
eye screening by sending the invitation letter or calls.
Since the cohort members of type 2 diabetics were derived from 1991-1993 and
received eye screening in 1999, variables associated with the risk of nephropathy
were collected in two occasions, including baseline variables collected in 1991-1993
and subsequent information accrued from nephropathy screening in 1999.
(1) Information from baseline survey (1991-1993)
In the baseline survey, personal interviews with a closed and structured
questionnaire, and measurements of biochemistry markers were carried out by the
Yang-Ming Crusade in Kinmen. Variables collected in the baseline survey included
fasting plasma glucose (FPG), blood pressure, disease history, etc.
(2) Follow-up information for nephropathy screening (1999)
In addition to the baseline variables, HbA1c was also collected for nephropathy
screening. Usning UKPDS criteria, high level of HbA1c was defined as ≧7%6.
(3) Screening and diagnosis for nephropathy
The random uric sample was collected. Development of nephropathy was defined
according to the urinary protein-to-creatinine ratio(UPCR)7-9: (1)normal <0.2, (2)
low-grade proteinuria 0.2≦UPCR <0.5,(3) ≧0.5 overt proteinuria. The duration of
diabetes was classified into four categories: <10 years, 10-12 years, 13-15 years, and
≧16 years.
(4) Statistical Analysis
In the univariate analysis, the independent t-test method was adopted to assess the
differences of the mean value of continuous variables between normal and
nephropathy. The logistic regression model was used to assess the effects of relevant
predictors after controlling for the covariates. Odds ratio and 95% confidence
intervals were used for categorical variables.
Results
Of 971 diabetic subjects, 578 subjects attended the screening. The overall
response rate was about 60%. Table 1 shows that female had higher response rate than
male, and the young adults aged 30-39 and old people over 70 year of age had lower
response rate than other age groups. The majority of baseline factors associated with
the risk of type 2 diabetes in attendants were similar to those in non-attendants except
that age of non-attendants (58.3 11.4yrs) were statistically significant older than
attendants (56.710.9yrs). Other baseline factors associated with the risk of type 2
diabetes for attendants were not significantly different from those for non-attendants.
Table 2 shows the prevalence of nephropathy among type 2 diabetics. 175 of 578
of diabetes were diagnosed with nephropathy, and the prevalence was 30.3 %,
including 18.0% of low-grade proteinuria and 12.3% of overt proteinuria. Male
(32.4%) was statistically higher than female (27.1%) (p<0.05). The prevalence of
low-grade proteinuria and overt proteinuria showed a increase with age.
Table 3 shows the univariate analysis of associated factors of proteinuria among
type 2 diabetic subjects. Significant factors associated with nephropathy were age at
diagnosed of type 2 diabetes (P<0.01), duration of diabetes ( P<0.01), systolic blood
pressure(P<0.01), HbA1c(P<0.01), fasting plasma glucose (P<0.01),.blood urea
nitrogen(P<0.01),HDL-C(P<0.01) and creatinine(P<0.01). The variables of no
significant different on proteinuria were body mass index, diastolic blood pressure,
total cholesterol, triglyceride and uric acid.
The effects of independent predictors of nephropathy were examined by the
multiple logistic regression model. Table 4 shows the independent predictors of
nephropathy. The significant associated factors for nephropathy were systolic blood
pressure, duration of diabetes, BUN, and HbA1c.Odds ratios for duration were
estimated as 1.53 (95%CI: 0.51-4.56) in 10-12 years, 9.50 (95%CI: 1.13-80.18) in
13-15 years, and 11.12(95%CI: 1.29-96.12) in ≧16 years compared with <10 years.
Figure 2 shows the prevalence of nephropathy. The prevalence of nephropathy of
subjects with <10 years duration of diabetes was 27.0%. The prevalence of
nephropathy of subjects with 10-12 years duration of diabetes was 39.1%. The
prevalence of nephropathy of subjects with 13-15 years duration of diabetes was
81.3%. The prevalence of nephropathy of subjects with ≧16 years duration of
diabetes was 80.0%. When the duration of diabetes was over 12 years the prevalence
of nephropathy will increase dramatically. And subjects with >12 years duration of
diabetes had more then two-folded risk for nephropathy as compared with the subjects
with ≦12 years duration of diabetes. The duration of diabetes could be an indicator
for the occurrence of nephropathy.
Discussion
From the preventive medicine viewpoint, conducting a community-based
screening for early nephropathy among type 2 diabetics is essential.
In the present study, the results provide an opportunity to elucidate the
associations between putative predictors and nephropathy. The significant predictors
in our study are congruent with biological plausibility. The impact of predictors on the
development of nephropathy are glyecemic control, higher blood urea nitrogen,
hypertension and the duration of diabetes. Many studies showed the same finding
10-16
.
Consistent with previous studies11,16, duration of diabetes was highly associated
with onset of nephropathy. This suggests that duration of diabetes is symbolic of an
indicator for deterioration of type 2 diabetes. This finding not only suggests that onset
of nephropathy may take 12 years after occurrence of type 2 diabetes, but also implies
that have a long period (not longer than 12 years) for early detection of nephropathy
whenever type 2 diabetes without nephropathy is detected.
High level of HbA1c revealed that poor glycemic controlled in type 2 diabetics. It
was strongly linked to nephropathy in the present study. This finding was also
consistent with early results in observational studies, a strong and consistent
relationship between glycemic controlled and the development of nephropathy 10, 12-15 .
SBP is also associated with nephropathy. It was also consistent with some studies 10,
12-15
. According to above, it is very import to control the level of HbA1c and treat
hypertension in type 2 diabetics.
Conclusions
This community-based screening for diabetic nephropathy displayed systolic blood
pressure, duration of diabetes, BUN, and HbA1c were the most important associated
factors. Duration of diabetes is an indicator for occurrence of nephropathy. The risk of
occurrence of nephropathy would increase rapidly when the duration of diabetes was
over 12 years.
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