title: Lower plasma creatinine and urine albumin in individuals at increased risk of type 2 diabetes with factor v leiden mutation.
abstract: The factor V Leiden (FVL) mutation is the most frequent genetic cause of venous thrombosis in Caucasians. However, protective effects have been suggested to balance the disadvantages. We have recently observed protective effects of FVL mutation on experimental diabetic nephropathy in mice as well as an association with reduced albuminuria in two human cohorts of diabetic patients. In the present study we aimed to reevaluate these findings in an independent, larger cohort of 1905 Caucasians at risk of developing type 2 diabetes and extend possible associations to earlier disease stages of nephropathy. Carriers of FVL mutation had a significantly lower urine albumin excretion (P = 0.03) and tended to have lower plasma creatinine concentrations (P = 0.07). The difference in plasma creatinine concentrations was significant after adjustment for the influencing factors: age, gender, and lean body mass (P = 0.048). These observations at a very early "disease" stage are an important extension of previous findings and suggest that modification of glomerular dysfunction by FVL mutation is relevant during very early stages of diabetic nephropathy. This makes the underlying mechanism an interesting therapeutic target and raises the question whether FVL mutation may also exert protective effects in other glomerulopathies.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls University Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany ; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, 72076 Tübingen, Germany ; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Andreas
authors.identifier: 0000-0001-5732-2287
authors.initials: A
authors.lastname: Peter
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls University Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany ; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, 72076 Tübingen, Germany ; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls University Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany ; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, 72076 Tübingen, Germany ; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.affiliation: German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany ; Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard-Karls University Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany ; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, 72076 Tübingen, Germany ; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Department of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, Germany.
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
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