Heli Viljakainen1, Kaisa K Ivaska, Päivi Paldánius, Marita Lipsanen-Nyman, Tero Saukkonen, Kirsi H Pietiläinen, Sture Andersson, Kalevi Laitinen, Outi Mäkitie. 1. Children's Hospital (H.V., P.P., M.L.-N., T.S., S.A., O.M.), Helsinki University Central Hospital, Obesity Research Unit (K.H.P.), Research Programs Unit, Diabetes and Obesity, University of Helsinki, and Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital and Institute for Molecular Medicine Finland, University of Helsinki, and Department of Obstetrics and Gynecology (K.L.), Helsinki University Central Hospital, FI-00029 Helsinki, Finland; Institute of Biomedicine (K.K.I.), Department of Cell Biology and Anatomy, University of Turku, FI-20520 Turku, Finland; Novartis Pharma (P.P.), CH-4002 Basel, Switzerland; Novo Nordisk Farma Oy (T.S.), FI-02240 Espoo, Finland; Folkhälsan Research Center (O.M.), FI-00250 Helsinki, Finland; and Department of Molecular Medicine and Surgery (O.M.), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Abstract
CONTEXT: Observations in rodents suggest that osteocalcin (OC) participates in glucose metabolism. Based on human studies, it remains unclear whether circulating OC is simply a bone turnover marker (BTM) or also a mediator in interactions between the skeleton and glucose homeostasis. OBJECTIVE: The objective of the study was to determine the responses of BTMs, including OC, to oral glucose tolerance test (OGTT) in a case-control setting. DESIGN AND PATIENTS: Thirty-four normoglycemic young adults [mean age 19 y (SD 2.3)] with severe childhood-onset obesity and their gender- and age-matched nonobese controls underwent a standard 2-hour OGTT. MAIN OUTCOME MEASURES: Glucose, insulin, and six BTMs including total and carboxylated OC (cOC) were determined at baseline and at 30, 60, 90, and 120 minutes during OGTT. RESULTS: The obese and control subjects were similar in height; the mean body mass indices were 40.4 and 21.9 kg/m(2), respectively. The homeostasis model assessment index was 2.7 times greater in the obese subjects. All BTMs, except bone-specific alkaline phophatase, were lower in the obese subjects compared with the controls: the differences at baseline were 40%, 35%, 17%, 31%, and 32% for N-terminal propeptides of type I collagen, cross-linked telopeptides of type I collagen, tartrate-resistant acid phosphatase, total OC, and carboxylated OC (P < .05 for all) after adjusting for whole-body bone area. All BTMs decreased during OGTT. The relative values for the OGTT responses for total, but not for cOC (measured as area under the curve) differed between the two groups (P = .029 and P = .139, respectively): the decrease in total OC during the OGTT was less pronounced in the obese subjects. Responses in other BTMs were similar between the groups. No associations were observed between glucose metabolism and OCs during OGTT with linear regression. CONCLUSIONS: Bone turnover markers were substantially lower in obese subjects compared with controls. Total OC and cOC showed less pronounced decrease during the OGTT in obese subjects compared with controls, whereas other BTMs responded similarly in the two groups. The role of OC, if anything, in glucose homeostasis is indirect and may be mediated via other factors than glucose or insulin.
CONTEXT: Observations in rodents suggest that osteocalcin (OC) participates in glucose metabolism. Based on human studies, it remains unclear whether circulating OC is simply a bone turnover marker (BTM) or also a mediator in interactions between the skeleton and glucose homeostasis. OBJECTIVE: The objective of the study was to determine the responses of BTMs, including OC, to oral glucose tolerance test (OGTT) in a case-control setting. DESIGN AND PATIENTS: Thirty-four normoglycemic young adults [mean age 19 y (SD 2.3)] with severe childhood-onset obesity and their gender- and age-matched nonobese controls underwent a standard 2-hour OGTT. MAIN OUTCOME MEASURES: Glucose, insulin, and six BTMs including total and carboxylated OC (cOC) were determined at baseline and at 30, 60, 90, and 120 minutes during OGTT. RESULTS: The obese and control subjects were similar in height; the mean body mass indices were 40.4 and 21.9 kg/m(2), respectively. The homeostasis model assessment index was 2.7 times greater in the obese subjects. All BTMs, except bone-specific alkaline phophatase, were lower in the obese subjects compared with the controls: the differences at baseline were 40%, 35%, 17%, 31%, and 32% for N-terminal propeptides of type I collagen, cross-linked telopeptides of type I collagen, tartrate-resistant acid phosphatase, total OC, and carboxylated OC (P < .05 for all) after adjusting for whole-body bone area. All BTMs decreased during OGTT. The relative values for the OGTT responses for total, but not for cOC (measured as area under the curve) differed between the two groups (P = .029 and P = .139, respectively): the decrease in total OC during the OGTT was less pronounced in the obese subjects. Responses in other BTMs were similar between the groups. No associations were observed between glucose metabolism and OCs during OGTT with linear regression. CONCLUSIONS: Bone turnover markers were substantially lower in obese subjects compared with controls. Total OC and cOC showed less pronounced decrease during the OGTT in obese subjects compared with controls, whereas other BTMs responded similarly in the two groups. The role of OC, if anything, in glucose homeostasis is indirect and may be mediated via other factors than glucose or insulin.
Authors: L N Mosca; T B L Goldberg; V N da Silva; C S Kurokawa; A C B Rizzo; C C da Silva; A Dos Santos Teixeira; J E Corrente Journal: Osteoporos Int Date: 2016-11-30 Impact factor: 4.507
Authors: R Saucedo; G Rico; G Vega; L Basurto; L Cordova; R Galvan; M Hernandez; E Puello; A Zarate Journal: J Endocrinol Invest Date: 2014-12-06 Impact factor: 4.256
Authors: Laura S Girão Lopes; Rubens Prado Schwartz; Bruno Ferraz-de-Souza; Maria Elizabeth Rossi da Silva; Pedro Henrique Silveira Corrêa; Márcia Nery Journal: Diabetol Metab Syndr Date: 2015-02-27 Impact factor: 3.320
Authors: Kaisa K Ivaska; Maikki K Heliövaara; Pertti Ebeling; Marco Bucci; Ville Huovinen; H Kalervo Väänänen; Pirjo Nuutila; Heikki A Koistinen Journal: Endocr Connect Date: 2015-06-05 Impact factor: 3.335
Authors: Heli Viljakainen; Johanna C Andersson-Assarsson; Miriam Armenio; Minna Pekkinen; Maria Pettersson; Helena Valta; Marita Lipsanen-Nyman; Outi Mäkitie; Anna Lindstrand Journal: PLoS One Date: 2015-07-01 Impact factor: 3.240
Authors: Satu Pirilä; Mervi Taskinen; Maila Turanlahti; Merja Kajosaari; Outi Mäkitie; Ulla M Saarinen-Pihkala; Heli Viljakainen Journal: PLoS One Date: 2014-10-13 Impact factor: 3.240