Blood sugar control reverses the increase in urinary excretion of prostaglandin D synthase in diabetic patients.
OBJECTIVE
We investigated basal levels of serum and urinary lipocalin-type prostaglandin D synthase/beta-trace (L-PGDS) in type-2 diabetic patients and explored whether glycemic control affects L-PGDS status in another 55 diabetic inpatients with normoalbuminuria.


METHODS
Fifty-five type-2 diabetic outpatients (HbA1c, 9.14 +/- 0.20%; creatinine (Cr), 85.1 +/- 2.4 micromol/l), and 55 age-matched healthy control subjects were recruited. Serum and urinary levels of L-PGDS were determined with respect to the stage of diabetic nephropathy. The L-PGDS was localized by immunohistochemistry.


RESULTS
The urinary L-PGDS index increased in diabetic patients, compared with the controls (234.8 +/- 27.4 vs. 73.8 +/- 7.8 microg/mmol Cr, p < 0.001). Even in normoalbuminuric patients as well as in microalbuminuric patients, urinary L-PGDS indexes were higher than the controls (166.0 +/- 21.1, p < 0.0001 and 338.6 +/- 62.5 microg/mmol Cr, p < 0.0001, respectively), although the serum L-PGDS level was equal to that in the control subjects. Multiple regression analysis revealed that the urinary L-PGDS index was predicted solely by glucose levels and type-IV collagen index, whereas the serum L-PGDS was determined mainly by age and serum Cr. Glycemic control reduced the urinary L-PGDS index towards the normal range in diabetic patients with normoalbuminuria (172.3 +/- 6.6 vs. 118.1 +/- 2.6 (SE) microg/mmol Cr, p < 0.0001). Immunohistochemistry showed that L-PGDS was uniquely present in the renal tubules in diabetes while in nondiabetics, L-PGDS occurred solely in the peritubular interstitium, not in the tubular cells.


CONCLUSIONS
Inadequate glycemic control is responsible for urinary L-PGDS excretion in the diabetic patients. Urinary L-PGDS is useful to predict subclinical renal injury associated with type-2 diabetes.
Department of Endocrinology and Metabolism, Kanto Medical Center NTT, Tokyo, Japan.
Kumiko
K
Hamano
Yasuo
Y
Totsuka
Miho
M
Ajima
Tomoko
T
Gomi
Toshio
T
Ikeda
Nobuhito
N
Hirawa
Yutaka
Y
Eguchi
Minoru
M
Yamakado
Masao
M
Takagi
Hiroshi
H
Nakajima
Hiroshi
H
Oda
Kousuke
K
Seiki
Naomi
N
Eguchi
Yoshihiro
Y
Urade
Yoshio
Y
Uehara
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000652:urine*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000652:urine; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000097:blood / Q000652:urine*; D007668:Kidney / Q000201:enzymology; D054834:Lipocalins; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
D001786:Blood Glucose; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase