TY - JOUR
T1 - Urinary platelet-activating factor excretion is elevated in non-insulin dependent diabetes mellitus
AU - Kudolo, George B.
AU - Defronzo, Ralph A.
N1 - Funding Information:
This work was supported by grants from the South Texas Health Research Center, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (DK51002–02) and M01-RR-01346. The nursing and dietetic care provided by the staff of the Frederic C. Bartter Clinical Research unit at the Audie L. Murphy Veteran’s Hospital is appreciated.
PY - 1999/5
Y1 - 1999/5
N2 - Proteinuria is currently considered a very sensitive predictor of diabetic nephropathy, but 20-25% of all diabetic patients with negative Albustix reaction excrete higher than normal (<20 mg/24 h) amounts of albumin in their urine. It is our hypothesis that platelet-activating factor (PAF), a potent glycerophospholipid that acts as a chemical mediator for a wide spectrum of biological activities, including increased vascular permeability, may be produced in significant amounts during periods preceding microalbuminuria. In this study, we compared urinary PAF excretion in Mexican-American subjects who were diagnosed with non-insulin dependent diabetes mellitus (NIDDM) with their healthy control counterparts. The age of the NIDDM subjects (45.9 ± 2.1 years) was not significantly different from the healthy control group, which was 39.4 ± 2.7 years (P<0.0672). The NIDDM subjects (body mass index, 29.9 ± 1.1 compared to 26.1 ± 0.9 kg/m2 in healthy controls) were characterized by significantly increased (P<0.05) fasting plasma glucose (192 ± 11 vs. 97 ± 4 mg/dl in healthy controls), fasting insulin (20.9 ± 2.4 vs. 12.3 ± 1.6 μU/ml), fasting C-peptide (2.93 ± 1.26 vs. 1.48 ± 0.51 ng/ml), and hemoglobin A(1c) (10.3 ± 0.7 vs. 5.6 ± 0.3%), respectively. The urine output for the NIDDM and control subjects were 1942 ± 191 ml/24 h and 1032 ± 94 ml/24 h, respectively, and urinary albumin excretion (UAE) rates were estimated to be 38 ± 7 μg/min and 11 ± 1 μg/min, respectively. The NIDDM subjects produced significantly increased levels of urinary PAF (2606.3 ± 513.1 ng/24 h compared with 77.9 ± 14.1 ng/24 h in controls (or 1706.3 ± 420.8 ng/ml compared with 85.4 ± 17.8 pg/ml of urine, in NIDDM and control subjects, respectively). We found that urinary PAF excretion was significantly correlated with microalbumin excretion (r = 0.7) especially at UAE rates greater than 30 mg/day and more importantly, some NIDDM patients with negative Albustix reaction (i.e, normal UAE) produced significantly more PAF, suggesting that PAF excretion may precede microalbuminuria and that subtle injury to the kidneys are present in NIDDM long before overt albuminuria ensues urinary PAF measurements could potentially therefore serve as a sensitive indicator of renal injury in diabetes mellitus. These results lend further credence to our hypothesis that PAF may be the biochemical compound linking the various members of the insulin resistance syndrome.
AB - Proteinuria is currently considered a very sensitive predictor of diabetic nephropathy, but 20-25% of all diabetic patients with negative Albustix reaction excrete higher than normal (<20 mg/24 h) amounts of albumin in their urine. It is our hypothesis that platelet-activating factor (PAF), a potent glycerophospholipid that acts as a chemical mediator for a wide spectrum of biological activities, including increased vascular permeability, may be produced in significant amounts during periods preceding microalbuminuria. In this study, we compared urinary PAF excretion in Mexican-American subjects who were diagnosed with non-insulin dependent diabetes mellitus (NIDDM) with their healthy control counterparts. The age of the NIDDM subjects (45.9 ± 2.1 years) was not significantly different from the healthy control group, which was 39.4 ± 2.7 years (P<0.0672). The NIDDM subjects (body mass index, 29.9 ± 1.1 compared to 26.1 ± 0.9 kg/m2 in healthy controls) were characterized by significantly increased (P<0.05) fasting plasma glucose (192 ± 11 vs. 97 ± 4 mg/dl in healthy controls), fasting insulin (20.9 ± 2.4 vs. 12.3 ± 1.6 μU/ml), fasting C-peptide (2.93 ± 1.26 vs. 1.48 ± 0.51 ng/ml), and hemoglobin A(1c) (10.3 ± 0.7 vs. 5.6 ± 0.3%), respectively. The urine output for the NIDDM and control subjects were 1942 ± 191 ml/24 h and 1032 ± 94 ml/24 h, respectively, and urinary albumin excretion (UAE) rates were estimated to be 38 ± 7 μg/min and 11 ± 1 μg/min, respectively. The NIDDM subjects produced significantly increased levels of urinary PAF (2606.3 ± 513.1 ng/24 h compared with 77.9 ± 14.1 ng/24 h in controls (or 1706.3 ± 420.8 ng/ml compared with 85.4 ± 17.8 pg/ml of urine, in NIDDM and control subjects, respectively). We found that urinary PAF excretion was significantly correlated with microalbumin excretion (r = 0.7) especially at UAE rates greater than 30 mg/day and more importantly, some NIDDM patients with negative Albustix reaction (i.e, normal UAE) produced significantly more PAF, suggesting that PAF excretion may precede microalbuminuria and that subtle injury to the kidneys are present in NIDDM long before overt albuminuria ensues urinary PAF measurements could potentially therefore serve as a sensitive indicator of renal injury in diabetes mellitus. These results lend further credence to our hypothesis that PAF may be the biochemical compound linking the various members of the insulin resistance syndrome.
KW - Albuminuria
KW - Non-insulin dependent diabetes mellitus
KW - Platelet-activating factor
UR - http://www.scopus.com/inward/record.url?scp=0033056733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033056733&partnerID=8YFLogxK
U2 - 10.1016/S0090-6980(98)00074-4
DO - 10.1016/S0090-6980(98)00074-4
M3 - Article
C2 - 10410380
AN - SCOPUS:0033056733
SN - 0090-6980
VL - 57
SP - 87
EP - 98
JO - Prostaglandins and Other Lipid Mediators
JF - Prostaglandins and Other Lipid Mediators
IS - 2-3
ER -