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Evaluation of placental growth factor and soluble Fms‐like tyrosine kinase 1 as predictors of all‐cause and cardiovascular mortality in patients with Type 1 diabetes with and without diabetic nephropathy
Author(s) -
Theilade S.,
Lajer M.,
Jorsal A.,
Tarnow L.,
Parving H.H.,
Rossing P.
Publication year - 2012
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2011.03482.x
Subject(s) - medicine , placental growth factor , renal function , diabetic nephropathy , diabetes mellitus , endocrinology , hazard ratio , soluble fms like tyrosine kinase 1 , type 2 diabetes , risk factor , kidney disease , nephropathy , gastroenterology , vascular endothelial growth factor , confidence interval , vegf receptors
Diabet. Med. 29, 337–344 (2012) Abstract Aims Placental growth factor is a vascular endothelial growth factor involved in angiogenesis, vascular inflammation and plaque formation. Soluble Fms‐like tyrosine kinase 1 is a decoy receptor for placental growth factor, reducing its activity. The aim of this study is to evaluate the predictive value of placental growth factor and soluble Fms‐like tyrosine kinase 1 in relation to all‐cause and cardiovascular mortality and decline in kidney function in Type 1 diabetes. Methods This was a prospective, observational follow‐up study with 8 (0–13) years [median (range)] of follow‐up, including patients with Type 1 diabetes, of whom 458 had diabetic nephropathy [278 men; age 42 ± 11 years (mean ± sd ), diabetes duration 28 ± 9 years, glomerular filtration rate 76 ± 33 ml min −1 1.73 m −2 ] and 442 had long‐standing normoalbuminuria (234 men; age 45 ± 12 years, diabetes duration 28 ± 10 years). Results Placental growth factor and soluble Fms‐like tyrosine kinase 1 levels measured at baseline were higher in patients with diabetic nephropathy compared with patients with long‐standing normoalbuminuria [median (range)] 15 (4–131) vs. 11 (7–64) ng/l, ( P < 0.001) and 86 (42–3462) vs. 77 (43–1557) ng/l ( P < 0.001), respectively. In patients with diabetic nephropathy, high levels of placental growth factor predicted all‐cause and cardiovascular mortality [hazard ratio 1.94 (1.16–3.24) and hazard ratio 2.91 (1.45–5.85)] after adjustment for sex, age, smoking, systolic blood pressure, HbA 1c , cholesterol, glomerular filtration rate and previous cardiovascular disease. High levels of placental growth factor predicted increased risk of end‐stage renal disease [hazard ratio 2.77 (1.47–5.14)], but covariate adjustments attenuated the association [hazard ratio 1.89 (0.91–3.95)]. Among patients with long‐standing normoalbuminuria, placental growth factor levels predicted fatal and non‐fatal cardiovascular events [hazard ratio 1.97 (1.03–3.76)], but not all‐cause mortality. Baseline soluble Fms‐like tyrosine kinase 1 levels did not predict outcome in either group after adjustment. Conclusion Placental growth factor is elevated in patients with Type 1 diabetes and diabetic nephropathy and predicts all‐cause and cardiovascular mortality, but not deterioration of kidney function.