V D F de Mello1, J Lindström2, J G Eriksson3, P Ilanne-Parikka4, S Keinänen-Kiukaanniemi5, J Pihlajamäki6, J Tuomilehto7, M Uusitupa8. 1. Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. Electronic address: vanessa.laaksonen@uef.fi. 2. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. 3. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Department of General Practice and Primary Health, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland; Vaasa Central Hospital, Vaasa, Finland. 4. The Diabetes Centre, Finnish Diabetes Association, Tampere, Finland; Science Center, Tampere University Hospital, Tampere, Finland. 5. Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of General Practice, Oulu University Hospital and Oulu Health Centre, Oulu, Finland. 6. Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland. 7. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Center for Vascular Prevention, Danube-University Krems, Austria. 8. Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Research Unit, Kuopio University Hospital, Kuopio, Finland.
Abstract
BACKGROUND AND AIMS: We examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention Study (DPS). We also explored a possible interaction of ABCG8 rs4299376 on sterol levels and lifestyle intervention. METHODS AND RESULTS: We conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994-2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had β-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in β-sitosterol and campesterol: 0.76 [0.63-0.92], and 0.81 [0.67-0.99], respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 [1.13-1.62]). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on β-sitosterol (p = 0.001) and campesterol (p = 0.004) levels during the follow-up. CONCLUSIONS: Markers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.
RCT Entities:
BACKGROUND AND AIMS: We examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention Study (DPS). We also explored a possible interaction of ABCG8rs4299376 on sterol levels and lifestyle intervention. METHODS AND RESULTS: We conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994-2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had β-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in β-sitosterol and campesterol: 0.76 [0.63-0.92], and 0.81 [0.67-0.99], respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 [1.13-1.62]). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on β-sitosterol (p = 0.001) and campesterol (p = 0.004) levels during the follow-up. CONCLUSIONS: Markers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.
Authors: Vanessa D de Mello; Jussi Paananen; Jaana Lindström; Maria A Lankinen; Lin Shi; Johanna Kuusisto; Jussi Pihlajamäki; Seppo Auriola; Marko Lehtonen; Olov Rolandsson; Ingvar A Bergdahl; Elise Nordin; Pirjo Ilanne-Parikka; Sirkka Keinänen-Kiukaanniemi; Rikard Landberg; Johan G Eriksson; Jaakko Tuomilehto; Kati Hanhineva; Matti Uusitupa Journal: Sci Rep Date: 2017-04-11 Impact factor: 4.379
Authors: Andrés Jiménez-Sánchez; Antonio Jesús Martínez-Ortega; Pablo Jesús Remón-Ruiz; Ana Piñar-Gutiérrez; José Luis Pereira-Cunill; Pedro Pablo García-Luna Journal: Nutrients Date: 2022-03-31 Impact factor: 5.717