title: The rs340874 PROX1 type 2 diabetes mellitus risk variant is associated with visceral fat accumulation and alterations in postprandial glucose and lipid metabolism.
abstract: Large-scale meta-analyses of genome-wide association studies have recently confirmed that the rs340874 single-nucleotide polymorphism in PROX1 gene is associated with fasting glycemia and type 2 diabetes mellitus; however, the mechanism of this link was not well established. The aim of our study was to evaluate the functional/phenotypic differences related to rs340874 PROX1 variants. The study group comprised 945 subjects of Polish origin (including 634 with BMI > 25) without previously known dysglycemia. We analyzed behavioral patterns (diet, physical activity), body fat distribution and glucose/fat metabolism after standardized meals and during the oral glucose tolerance test. We found that the carriers of the rs340874 PROX1 CC genotype had higher nonesterified fatty acids levels after high-fat meal (p = 0.035) and lower glucose oxidation (p = 0.014) after high-carbohydrate meal in comparison with subjects with other PROX1 genotypes. Moreover, in subjects with CC variant, we found higher accumulation of visceral fat (p < 0.02), but surprisingly lower daily food consumption (p < 0.001). We hypothesize that lipid metabolism alterations in subjects with the PROX1 CC genotype may be a primary cause of higher glucose levels after glucose load, since the fatty acids can inhibit insulin-stimulated glucose uptake by decreasing carbohydrate oxidation. Our observations suggest that the PROX1 variants have pleiotropic effect on disease pathways and it seem to be a very interesting goal of research on prevention of obesity and type 2 diabetes mellitus. The study may help to understand the mechanisms of visceral obesity and type 2 diabetes mellitus risk development.
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.|Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Kretowski
authors.affiliation: Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Adamska
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Maliszewska
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Wawrusiewicz-Kurylonek
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.|Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Citko
authors.affiliation: Centre for Experimental Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Goscik
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.|Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Bauer
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.
authors.forename: Juliusz
authors.initials: J
authors.lastname: Wilk
authors.affiliation: Department of Dietetics and Nutrition, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Golonko
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.|Department of Dietetics and Nutrition, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Waszczeniuk
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Lipinska
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Hryniewicka
authors.affiliation: Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Niemira
authors.affiliation: Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Paczkowska
authors.affiliation: Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Ciborowski
authors.affiliation: Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, M.C. Sklodowskiej-Curie 24A, 15-276 Bialystok, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Gorska