Urinary transforming growth factor-beta1 and alpha1-microglobulin in children and adolescents with type 1 diabetes.
OBJECTIVE
Transforming growth factor (TGF)-beta1 is an important mediator in the pathogenesis of diabetic nephropathy. Urinary TGF-beta1 reflects TGF-beta1 production in the kidney, and alpha1-microglobulin tubular dysfunction. These 2 markers were studied in the early phases of type 1 diabetes.


METHODS
There were 113 type 1 diabetic children and adolescents (mean +/- SD: age 14.1 +/- 2.9 years, and diabetes duration 7.4 +/- 2.9 years, HbA1c 9.3 +/- 1.5%) and 39 healthy subjects (age 13.8 +/- 2.8 years) who participated in the study. Of the diabetic patients, 105 were normoalbuminuric (2-3 consecutive overnight urinary albumin excretion rates [AERs] <20 microg/min) and 8 had microalbuminuria (at least 2 AERs 20-200 microg/min). Overnight urinary TGF-beta1 and alpha1-microglobulin levels were measured and the results expressed as the ratio to urinary creatinine concentration.


RESULTS
Data are medians (range). Diabetic patients had higher urinary TGF-beta1 levels than those of control subjects: 0.9 ng/mg (0.05-122.3) vs. 0.3 ng/mg (0.05-2.2) creatinine, respectively (P = 0.003). Urinary TGF-beta1 levels correlated with urinary glucose (r = 0.2, P = 0.03) and alpha1-microglobulin (r = 0.2, P = 0.02) levels, but not with HbA1c, AER, age, or duration of diabetes. In 43 patients with urinary TGF-beta1 above the control levels, urinary TGF-beta1 levels correlated with urinary glucose (r = 0.6, P < 0.001) and alpha1-microglobulin (r = 0.6, P < 0.001) levels. Diabetic patients had higher urinary alpha1-microglobulin levels than those of control subjects: 4.8 microg/mg (0.6-48.8) vs. 2.7 microg/mg (0.8-11.6) creatinine, respectively (P < 0.001). Alpha1-microglobulin levels correlated with AER (r = 0.2, P = 0.02), HbA1c (r = 0.3, P = 0.001), urinary glucose (r = 0.5, P < 0.001), and urinary TGF-beta1 levels.


CONCLUSIONS
An early rise in urinary TGF-beta1 levels was observed in young type 1 diabetic patients. Urinary TGF-beta1 is associated with 2 interrelated tubular markers, alpha1-microglobulin and urinary glucose.
Korpinen
E
E
Hospital for Children and Adolescents, University of Helsinki, Finland. eija.korpinen@hus.fi
Teppo
A M
AM
Hukkanen
L
L
Akerblom
H K
HK
Grönhagen-Riska
C
C
Vaarala
O
O
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000652:urine; D002648:Child; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D005260:Female; D006023:Glycoproteins / Q000652:urine*; D006029:Glycosuria / Q000652:urine; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D012016:Reference Values; D015842:Serine Proteinase Inhibitors / Q000652:urine*; D016212:Transforming Growth Factor beta / Q000652:urine*; D014360:Trypsin Inhibitor, Kunitz Soybean
D006023:Glycoproteins; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; D015842:Serine Proteinase Inhibitors; D016212:Transforming Growth Factor beta; D014360:Trypsin Inhibitor, Kunitz Soybean; D003404:Creatinine