Although microalbuminuria is considered as an early marker of nephropathy in diabetic adults, available information in diabetic adolescents is limited. The aim of this study was to investigate prevalence and frequency of regression of microalbuminuria in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients with childhood onset.
One hundred and nine adolescents (median, 18.9 years; interquartile range (IQR), 16.5-21.0 years) with T1DM and 18 T2DM adolescents (median, 17.9 years; IQR, 16.8-18.4 years) with repeated measurements of microalbuminuria (first morning urine microalbumin/creatinine ratios) were included. The median duration of diabetes was 10.1 (7.8-14.0) years and 5.0 (3.5-5.6) years, respectively, and follow-up period ranged 0.5-7.0 years. Growth parameters, estimated glomerular filtration rate, glycosylated hemoglobin (HbA1c) and lipid profiles were obtained after reviewing medical record in each subject.
The prevalence of microalbuminuria at baseline and evaluation were 21.1% and 17.4% in T1DM, and 44.4% and 38.9% in T2DM. Regression of microalbuminuria was observed in 13 T1DM patients (56.5%) and 3 T2DM patients (37.5%), and progression rate was 10.5% and 20% in T1DM and T2DM respectively. In regression T1DM group, HbA1c at baseline and follow-up was lower, and C-peptide at baseline was higher compared to persistent or progression groups. In T2DM, higher triglyceride was observed in persistent group.
Considerable regression of microalbuminuria more than progression in diabetes adolescents indicates elevated urinary microalbumin excretion in a single test does not imply irreversible diabetic nephropathy. Careful monitoring and adequate intervention should be emphasized in adolescents with microalbuminuria to prevent rapid progression toward diabetic nephropathy.
Microalbuminuria is known as an early marker of nephropathy and cardiovascular diseases in adults with diabetes
Regression of microalbuminuria was reported in type 1 diabetes adults that occurred in 58% of the patients with a 6-year cumulative incidence of microalbuminuria, and modifiable factors were low glycosylated hemoglobin (HbA1c) levels, low blood pressure and low levels of lipid concentration
It was also reported that 72% of type 1 diabetic children had regression to normoalbuminuria using repeated random spot urine tests in a single center study
In this study, we investigated prevalence and frequency of regression of microalbuminuria in adolescents with childhood onset type 1 (T1DM) and type 2 diabetes mellitus (T2DM).
A total of 127 patients (83 males and 44 females, 8-28 years) with childhood onset T1DM or T2DM, who visited department of pediatrics, Konkuk University Medical Center and Childhood Diabetes Clinic of Severance Children's Hospital were included from July 2007 to July 2014. One hundred and nine patients were T1DM and 18 patients were T2DM. Diabetic patients with macroalbuminuria or overt proteinuria, hematuria, menstrual bleeding, infections, fever, and other renal diseases were excluded. Confirmed cases of diabetic nephropathy treated with medication were also excluded in this study.
Height and body weight were measured with a stadiometer and a calibrated digital electric scale, and body mass index (BMI) was calculated in each subject. The
First morning urine sample was obtained in all patients, with an average of 2.7 urine samples per a patient. Three or more urine samples were collected in 24.4% and 2 samples collected in 75.6% of the patients. Baseline was the time of initial measurement of microalbuminuria, not meant by the time of diagnosis as diabetes. Follow-up was the time of last measurement of microalbuminuria. Spot urine microalbumin/creatinine ratio (mg/g) was measured by the Jaffe method, and microalbuminuria is defined as 30-300 mg/g of microalbumin/creatinine ratio in spot urine
Medical record was reviewed retrospectively in each patient.
This study was approved by the Institutional Review Board of Konkuk University Medical Center, Seoul, Korea (IRB No. KUH1090029).
Data are expressed as median (interquartile range [IQR] or range), or number and proportion (%). Standard descriptive statistics were used to summarize demographic and laboratory variables. Changes in variables between baseline and follow-up were tested using the Wilcoxon signed-rank test. Mann-Whitney
One hundred and nine patients were T1DM (39 males and 70 females) and 18 patients were T2DM (4 males and 14 females). The median duration of diabetes was 10.1 years and 5.0 years, respectively (
The prevalence of microalbuminuria at baseline and follow up were 21.1% and 17.4% in T1DM, and 44.4% and 38.9% in T2DM (
Clinical characteristics and laboratory parameters of T1DM and T2DM patients were compared among persistent, regression, progression, and normoalbuminuria groups (
The prevalence of microalbuminuria at baseline and follow-up were 21.1% and 17.4% in T1DM, and 44.4% and 38.9% in T2DM. The regression of microalbuminuria was observed in 56.5% of T1DM patients and 37.5% of T2DM patients during follow-up. Lower baseline HbA1c (persistent vs. regression,
While microalbuminuria was considered as a predictor of diabetic nephropathy in both adults and children
In patients with T2DM, microalbuminuria might be an early marker of T2DM, and it could precede a diagnosis of T2DM
Our study has limitations. First, retrospective nature of study design is a limitation. Second, although important clinical and laboratory determinants of microalbuminuria were measured in the present study, other affecting factors such as blood pressure, sodium intake, and the use of angiotensin converting enzyme inhibitors or angiotensin receptor blocker were not included as a variable. Third, small sample size and short follow-up period is another limitation. During annual or biannual screening of microalbuminuria according to clinical practice guideline, frequent regression of microalbuminuria in both T1DM and T2DM patients was observed
Variable | T1DM (n=109) |
T2DM (n=18) |
||
---|---|---|---|---|
Baseline | Follow-up | Baseline | Follow-up | |
Anthropometric index | ||||
Age (yr) | 17.5 |
18.9 (16.5–21.0) | 15.4 |
17.9 (16.8–18.4) |
Sex, male/female | 39/70 | 4/14 | ||
Diabetes duration (yr) | 9.5 |
10.1 (7.8–14.0) | 0.9 |
5.0 (3.5–5.6) |
Height (cm) | 162.0 |
162.9 (160.0–172.0) | 158.5 |
160.2 (153.5–163.2) |
Weight (kg) | 57.0 |
58.5 (54.0–65.0) | 61.0 (54.0–73.7) | 63.4 (54.0–75.5) |
BMI (kg/m2) | 21.52 |
21.91 (20.03–23.41) | 24.74 (21.09–30.88) | 24.31 (21.09–29.02) |
Height |
0.12 |
0.05 (–0.55 to 0.86) | 0.50 |
–0.10 (–1.45 to 0.13) |
Weight |
0.31 (–0.17 to 1.00) | 0.27 (–0.17 to 1.02) | 1.02 |
0.35 (–0.01 to 2.17) |
BMI |
0.31 (–0.43 to 0.78) | 0.30 (–0.43 to 0.83) | 1.29 (–0.02 to 2.49) | 0.99 (–0.01 to 2.27) |
Biochemical profiles | ||||
Serum creatinine (mg/dL) | 0.80 (0.70–0.90) | 0.75 (0.69–0.85) | 0.80 (0.60–0.90) | 0.65 (0.60–0.76) |
eGFR (mL/min/1.73 m2) | 125.7 (110.0–134.6) | 127.9 |
128.5 (109.9–156.3) | 139.6 (129.0–152.1) |
Urine microalbumin/creatinine (mg/g) | 9.4 (6.3–26.6) | 13.3 (8.6–24.8) | 25.3 (11.5–56.0) | 17.7 (6.2–42.0) |
Cholesterol (mg/dL) | 175.0 (167.0–230.0) | 179.0 (163.0–206.0) | 194.0 (161.0–231.0) | 150.0 (139.0–222.0) |
TG (mg/dL) | 79.0 (61.0–101.0) | 74.0 (56.0–93.0) | 105.0 (85.0–235.0) | 92.0 (64.0–262.0) |
HDL-cholesterol (mg/dL) | 58.0 (50.0–68.0) | 60.0 |
49.5 (43.0–52.0) | 53.0 (45.0–59.0) |
HbA1c (%) | 8.3 (7.3–9.6) | 8.4 (7.4–9.6) | 8.8 (6.9–12.2) | 7.8 (6.2–11.7) |
C-peptide (ng/mL) | 0.02 (0.015–0.039) | 0.02 (0.015–0.018) | 2.97 |
1.96 (1.432–2.393) |
Values are presented as median (interquartile range) or number.
T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; BMI, body mass index; eGFR, estimated glomerular filtration rate; TG, triglyceride; HDL-cholesterol, high density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; C-peptide, connecting peptide.
Characteristic | Persistent (n=10) |
Regression (n=13) |
Progression (n=9) |
Normal (n=77) |
||||
---|---|---|---|---|---|---|---|---|
Baseline | Follow-up | Baseline | Follow-up | Baseline | Follow-up | Baseline | Follow-up | |
Anthropometric index | ||||||||
Age (yr) | 17.8 (14.5-22.5) | 19.2 (17.0-23.0) | 17.0 (15.0-21.0) | 20.0 (17.5-21.5) | 19.0 (19.0-24.5) | 20.0 (19.5-25.0) | 17.5 (15.0-20.5) | 18.0 (15.5-21.0) |
Sex, male/female | 2/8 | 4/9 | 3/6 | 4/9 | ||||
Diabetes duration (yr) | 12.0 (7.5-16.0) | 12.8 (8.0-16.5) | 10.0 (5.0-11.1) | 10.5 (7.9-13.0) | 11.5 (5.5-15.0) | 12.0 (7.5-16.0) | 9.5 (6.5-13.5) | 10.0 (7.0-14.0) |
Follow-up duration (yr) | 0.5 (0.5-1.0) |
1.0 (0.5-4.0) | 0.5 (0.5–1.0) |
1.0 (0.5-0.5) | ||||
Height |
0.10 (-0.15-0.63) | 0.11 (-0.15 to 0.53) | -0.15 (-0.41 to 0.28) | -0.22 (-0.55 to 0.26) | 0.01 (-0.15 to 0.25) | -0.01 (-0.15 to 0.25) | 0.24 (-0.55 to 1.02) | 0.15 (-0.55 to 0.86) |
Weight |
0.67 (0.32-1.13) | 0.68 (0.04-1.02) | 0.42 (-0.10-0.71) | 0.22 (-0.09 to 1.13) | 0.08 (-0.02 to 0.79) | 0.08 (-0.02 to 0.79) | 0.29 (-0.17 to 0.90) | 0.29 (-0.17 to 0.90) |
BMI |
0.55 (0.28-0.83) | 0.51 (0.12-0.83) | 0.39 (-0.12 to 0.76) | 0.34 (0.30-0.68) | -0.04 (-0.47 to 0.77) | -0.04 (-0.11 to 0.77) | 0.28 (-0.50 to 0.59) | 0.25 (-0.50 to 0.59) |
Biochemical profiles | ||||||||
sCr (mg/dL) | 0.70 (0.60-0.90) | 0.69 (0.65-0.74) | 0.80 (0.70-1.00) | 0.73 (0.69-0.99) | 0.78 (0.60-0.80) | 0.75 (0.74-0.81) | 0.80 (0.70-0.90) | 0.76 (0.69-0.86) |
eGFR (mL/min/1.73 m2) | 127.7 (110.0-165.0) | 129.5 (125.3-156.6) | 116.3 (99.4-127.3) | 128.3 (119.3-135.4) | 117.3 (116.9-148.5) | 118.8 (116.5-128.8) | 125.7 (110.0-133.6) | 127.5 (117.0-136.1) |
Urine microalbumin/creatinine (mg/g) | 63.3 (48.9-171.8) | 58.0 (48.0-92.4) | 56.4 (34.1-74.0) | 9.6 (8.6-15.8) | 15.4 (11.4-22.0) | 42.1 (30.8-50.2) | 7.4 (5.0-10.1) | 11.3 (7.8-16.5) |
Cholesterol (mg/dL) | NA | NA | 175.0 (160.0-214.0) | 168.0 (163.0-206.0) | NA | NA | 181.0 (175.0-187.0) | 177.5 (160.0-195.0) |
TG (mg/dL) | 70.0 (64.0-135.0) | 75.0 (68.0-119.0) | 79.5 (67.0-109.0) | 77.5 (73-94) | 92.0 (81-94) | 71.0 (61-89) | 76.0 (56-99) | 67.0 (53-91) |
HDL-cholesterol (mg/dL) | 58.0 (56.0-64.0) | 55.0 (53.0-66.0) | 58.0 (53.0-67.0) | 61.5 (55.0-68.0) | 56.0 (45.0-68.0) | 60.0 (47.0-75.0) | 58.0 (49.0-67.0) | 60.0 (52.0-68.0) |
HbA1c (%) | 9.8 (8.7-13.8) |
9.7 (8.9-10.1) |
8.0 (7.0-8.9) |
8.0 (7.1-9.4) |
9.6 (8.5-10.2) | 9.5 (7.8-10.1) | 8.2 (7.1-9.1) | 8.1 (7.2-9.0) |
C-peptide (ng/mL) | 0.02 (0.015-0.015) | 0.02 (0.015-0.018) | 0.27 (0.015-0.571) |
0.02 (0.020-0.050) | 0.03 (0.015-0.100) |
0.04 (0.020-0.092) | 0.02 (0.015-0.020) | 0.02 (0.015-0.022) |
Values are presented as median (interquartile range or range) or number.
T1DM, type 1 diabetes mellitus; BMI, body mass index; sCr, serum creatinine; eGFR, estimated glomerular filtration rate; TG, triglyceride; HDL-cholesterol, high density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; C-peptide, connecting peptide; NA, not available.
Characteristic | Persistent (n=5) |
Regression (n=3) |
Progression (n=2) |
Normoalbuminuria (n=8) |
||||
---|---|---|---|---|---|---|---|---|
Baseline | Follow-up | Baseline | Follow-up | Baseline | Follow-up | Baseline | Follow-up | |
Anthropometric index | ||||||||
Age (yr) | 14.9 (13.3-16.8) | 17.9 (17.8-18.1) | 14.1 (11.9-26.0) | 18.2 (13.8-27.0) | 18.9 (15.8-22.0) | 19.7 (16.8-22.5) | 14.4 (12.3-17.4) | 17.0 (15.8-18.4) |
Sex, male/female | 0/3 | 0/5 | 0/2 | 4/4 | ||||
Diabetes duration (yr) | 2.6 (0.2-3.0) | 5.6 (5.3-6.6) | 0.0 (0.0-13.0) | 4.1 (1.9-14.0) | 2.3 (0.5-4.0) | 3.0 (1.0-5.0) | 0.7 (0.0-3.0) | 4.6 (3.2-5.1) |
Follow-up duration (yr) | 4.4 (3.0-5.1) | 1.9 (1.0-4.1) | 0.8 (0.5-1.0) | 2.6 (0.5-5.0) | ||||
Height |
0.00 (-0.02 to 0.01) |
-0.02 (-1.45 to -0.01) | -0.15 (-0.55 to 0.05) | -0.63 (-0.79 to -0.15) | -1.92 (-2.23 to -1.60) | -1.92 (-2.23 to -1.61) | 0.65 (0.46-0.98) | 0.12 (-0.70 to 0.47) |
Weight |
2.33 (1.18-2.50) | 1.56 (1.47-2.38) | -0.15 (-2.16 to -0.02) | -0.02 (-3.07-0.04) | 0.20 (0.13-0.27) | 0.20 (0.13-0.27) | 1.74 (0.31-2.68) | 0.63 (-0.01 to 2.29) |
BMI |
2.10 (1.28-2.85) | 2.27 (1.57-2.35) | -0.26 (-2.39 to -0.02) | -0.02 (-2.97 to 0.49) | 1.16 (1.00-1.31) | 1.13 (0.94-1.31) | 1.83 (-0.07 to 2.57) | 0.99 (-0.16 to 2.27) |
Biochemical profiles | ||||||||
sCr (mg/dL) | 0.80 (0.58-0.90) | 0.59 (0.49-0.64) | 0.80 (0.52-1.10) | 0.62 (0.55-0.76) | 0.63 (0.60-0.65) | 0.71 (0.66-0.76) | 0.85 (0.65-0.90) | 0.75 (0.61-0.81) |
eGFR (mL/min/1.73 m2) | 110.3 (99.3-151.9) | 152.1 (131.8-180.4) | 115.8 (77.5-158.7) | 136.2 (110.0-157.5) | 132.9 (128.2-137.5) | 117.7 (108.6-126.8) | 131.3 (109.9-181.5) | 145.2 (131.1-148.6) |
Urine microalbumin/creatinine (mg/g) | 63.48 (40.18-117.46) | 68.59 (42.04-72.26) | 56.00 (34.29-241.43) | 15.29 (13.23-20.02) | 6.21 (3.55-8.88) | 38.76 (30.20-47.32) | 13.16 (9.29-21.32) | 5.96 (3.83-9.13) |
Cholesterol (mg/dL) | 218.0 (194-253) | 209.0 (147-338) | 196.0 (161-231) | 174.0 (160-188) | NA | NA | 162.0 (136-165) | 139.0 (136-141) |
TG (mg/dL) | 295.0 (179-581) |
326.0 (320-572) |
87.0 (85-251) | 95.0 (60-149) | 181.0 (127-235) | 215.0 (168-262) | 68.5 (55-106) | 64.0 (60-82) |
HDL-cholesterol (mg/dL) | 52.0 (51-52) | 54.0 (45-57) | 64.0 (41-73) | 59.0 (44-64) | 39.5 (35-44) | 43.5 (41-46) | 47.5 (43-50) | 53.0 (45-66) |
HbA1c (%) | 11.2 (7.0-12.2) | 11.1 (8.2-12.3) | 13.3 (7.6-15.0) | 6.3 (6.1-12.1) | 6.7 (6.1-7.3) | 7.8 (6.4-9.2) | 8.3 (5.6-11.1) | 6.6 (5.4-11.7) |
C-peptide (ng/mL) | 3.73 (2.710-3.750) | 2.25 (1.960-3.100) | 2.08 (1.010-2.230) | 2.43 (1.420-3.440) | 3.41 (2.470-4.340) | 1.83 (1.270-2.390) | 3.00 (2.970-3.200) | 1.63 (1.180-2.130) |
Values are presented as median (interquartile range or range) or number.
T2DM, type 2 diabetes mellitus; BMI, body mass index; sCr, serum creatinine; eGFR, estimated glomerular filtration rate; TG, triglyceride; HDL-cholesterol, high density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; C-peptide, connecting peptide; NA, not available.