Maren Carstensen-Kirberg1,2, Erifili Hatziagelaki3, Anastasia Tsiavou3, Athina Chounta4, Peter Nowotny1,2, Giovanni Pacini5, George Dimitriadis3, Michael Roden1,2,6, Christian Herder1,2. 1. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 2. German Center for Diabetes Research (DZD), München-Neuherberg, Germany. 3. 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, 'Attikon' University General Hospital, Athens, Greece. 4. 4th Department of Internal Medicine, 'Attikon' University General Hospital, Athens, Greece. 5. Metabolic Unit, CNR Neuroscience Institute, National Research Council, Padova, Italy. 6. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Abstract
BACKGROUND: Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans. MATERIAL AND METHODS: This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT. RESULTS: Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index. CONCLUSIONS: The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.
BACKGROUND: Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans. MATERIAL AND METHODS: This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT. RESULTS: Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index. CONCLUSIONS: The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.
Authors: Nguyen Linh Toan; Nguyen Van Hoan; Doan Viet Cuong; Nguyen Viet Dung; Phan The Dung; Ngo Thu Hang; Do Thi Huyen Dieu; Dang Thanh Chung; Ho Anh Son; Pham Xuan Phong; George Binh Lenon; Doan Van De; Hoang Van Tong Journal: Diabetol Metab Syndr Date: 2018-05-15 Impact factor: 3.320
Authors: Anny H Xiang; Mary Helen Black; Yu-Hsiang Shu; Jun Wu; Adrienne MacKay; Corinna Koebnick; Richard M Watanabe; Thomas A Buchanan Journal: PLoS One Date: 2018-08-13 Impact factor: 3.240