Anne-Frédérique Turcotte1,2, Thomas Grenier-Larouche3,4, Julie Lacombe5, Anne-Marie Carreau1,2, André C Carpentier3,4, Fabrice Mac-Way1,2, André Tchernof1,2,6, Denis Richard2,6, Laurent Biertho6,7, Stefane Lebel6,7, Simon Marceau6,7, Mathieu Ferron5,8, Claudia Gagnon9,10,11,12. 1. Endocrinology and Nephrology Unit, CHU de Québec-Université Laval Research Centre, Québec City, QC, Canada. 2. Department of Medicine, Laval University, Québec City, QC, Canada. 3. Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Sherbrooke, QC, Canada. 4. Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. 5. Institut de recherches cliniques de Montréal, Montreal, QC, Canada. 6. Québec Heart and Lung Institute Research Centre, Québec City, QC, Canada. 7. Department of Surgery, Laval University, Québec City, QC, Canada. 8. Department of Medicine, Université de Montréal, Montreal, QC, Canada. 9. Endocrinology and Nephrology Unit, CHU de Québec-Université Laval Research Centre, Québec City, QC, Canada. claudia.gagnon@crchudequebec.ulaval.ca. 10. Department of Medicine, Laval University, Québec City, QC, Canada. claudia.gagnon@crchudequebec.ulaval.ca. 11. Québec Heart and Lung Institute Research Centre, Québec City, QC, Canada. claudia.gagnon@crchudequebec.ulaval.ca. 12. Institute of Nutrition and Functional Foods, Université Laval, Quebec City, QC, Canada. claudia.gagnon@crchudequebec.ulaval.ca.
Abstract
PURPOSE: Bone may regulate glucose homeostasis via uncarboxylated bioactive osteocalcin (ucOCN). This study explored whether changes in ucOCN and bone remodeling are associated with change in glucose homeostasis after biliopancreatic diversion (BPD). METHODS: In this secondary exploratory analysis of a 1-year prospective observational study, 16 participants (11 men/5 women; 69% with type 2 diabetes; mean BMI 49.4 kg/m2) were assessed before, 3 days, 3 months and 12 months after BPD. Changes in plasma ucOCN and bone markers (C-terminal telopeptide (CTX), total osteocalcin (OCN)) were correlated with changes in insulin resistance or sensitivity indices (HOMA-IR; adipose tissue insulin resistance index (ADIPO-IR) and insulin sensitivity index (SI) from the hyperinsulinemic-euglycemic clamp), insulin secretion rate (ISR) from the hyperglycemic clamp, and disposition index (DI: SI × ISR) using Spearman correlations before and after adjustment for weight loss. RESULTS: ucOCN was unchanged at 3 days but increased dramatically at 3 months (+257%) and 12 months (+498%). Change in ucOCN correlated significantly with change in CTX at 3 months (r = 0.62, p = 0.015) and 12 months (r = 0.64, p = 0.025) before adjustment for weight loss. It also correlated significantly with change in fasting insulin (r = -0.53, p = 0.035), HOMA-IR (r = -0.54, p = 0.033) and SI (r = 0.52, p = 0.041) at 3 days, and ADIPO-IR (r = -0.69, p = 0.003) and HbA1c (r = -0.69, p = 0.005) at 3 months. Change in OCN did not correlate with any glucose homeostasis indices. Results were similar after adjustment for weight loss. CONCLUSION: The increase in ucOCN may be associated with the improvement in insulin resistance after BPD, independently of weight loss. These findings need to be confirmed in larger, less heterogeneous populations.
PURPOSE: Bone may regulate glucose homeostasis via uncarboxylated bioactive osteocalcin (ucOCN). This study explored whether changes in ucOCN and bone remodeling are associated with change in glucose homeostasis after biliopancreatic diversion (BPD). METHODS: In this secondary exploratory analysis of a 1-year prospective observational study, 16 participants (11 men/5 women; 69% with type 2 diabetes; mean BMI 49.4 kg/m2) were assessed before, 3 days, 3 months and 12 months after BPD. Changes in plasma ucOCN and bone markers (C-terminal telopeptide (CTX), total osteocalcin (OCN)) were correlated with changes in insulin resistance or sensitivity indices (HOMA-IR; adipose tissue insulin resistance index (ADIPO-IR) and insulin sensitivity index (SI) from the hyperinsulinemic-euglycemic clamp), insulin secretion rate (ISR) from the hyperglycemic clamp, and disposition index (DI: SI × ISR) using Spearman correlations before and after adjustment for weight loss. RESULTS: ucOCN was unchanged at 3 days but increased dramatically at 3 months (+257%) and 12 months (+498%). Change in ucOCN correlated significantly with change in CTX at 3 months (r = 0.62, p = 0.015) and 12 months (r = 0.64, p = 0.025) before adjustment for weight loss. It also correlated significantly with change in fasting insulin (r = -0.53, p = 0.035), HOMA-IR (r = -0.54, p = 0.033) and SI (r = 0.52, p = 0.041) at 3 days, and ADIPO-IR (r = -0.69, p = 0.003) and HbA1c (r = -0.69, p = 0.005) at 3 months. Change in OCN did not correlate with any glucose homeostasis indices. Results were similar after adjustment for weight loss. CONCLUSION: The increase in ucOCN may be associated with the improvement in insulin resistance after BPD, independently of weight loss. These findings need to be confirmed in larger, less heterogeneous populations.
Authors: Geltrude Mingrone; Simona Panunzi; Andrea De Gaetano; Caterina Guidone; Amerigo Iaconelli; Laura Leccesi; Giuseppe Nanni; Alfons Pomp; Marco Castagneto; Giovanni Ghirlanda; Francesco Rubino Journal: N Engl J Med Date: 2012-03-26 Impact factor: 91.245
Authors: Henry Buchwald; Rhonda Estok; Kyle Fahrbach; Deirdre Banel; Michael D Jensen; Walter J Pories; John P Bantle; Isabella Sledge Journal: Am J Med Date: 2009-03 Impact factor: 4.965