The role of enteric hormone GLP-2 in the response of bone markers to a mixed meal in postmenopausal women with type 2 diabetes mellitus

Diabetology & Metabolic Syndrome

Márcia Nery⁴  Pedro Henrique Silveira Corrêa³  Maria Elizabeth Rossi da Silva²  Bruno Ferraz-de-Souza³  Rubens Prado Schwartz¹  Laura S Girão Lopes⁴ 

[1] Instituto de Radiologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;Laboratório de Carboidratos e Radioimunoensaios/LIM-18, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;Unidade de Doenças Osteometabólicas do Serviço de Endocrinologia e Metabologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil;Unidade de Diabetes, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

关键词: Osteocalcin;    CTX;    GLP-2;    Mixed meal;    Type 2 diabetes mellitus;    Bone remodeling;   

Others  :  1136503
DOI  :  10.1186/s13098-015-0006-7

 received in 2014-11-21, accepted in 2015-02-09,  发布年份 2015

【 摘 要 】

Background

Type 2 diabetes mellitus (T2D) is a complex disease associated with several chronic complications, including bone fragility and high fracture risk due to mechanisms not yet fully understood. The influence of the gastrointestinal tract and its hormones on bone remodeling has been demonstrated in healthy individuals. Glucagon-like peptide 2 (GLP-2), an enteric hormone secreted in response to nutrient intake, has been implicated as a mediator of nutrient effects on bone remodeling. This study aimed to analyze the dynamics of bone resorption marker C-terminal telopeptide of type I collagen (CTX), bone formation marker osteocalcin, and GLP-2 in response to a mixed meal in diabetic postmenopausal women.

Methods

Forty-three postmenopausal women with osteopenia or osteoporosis (20 controls – group CO – and 23 diabetic – group T2D) were subjected to a standard mixed meal tolerance test, with determination of serum CTX, plasma osteocalcin and serum GLP-2 concentrations at baseline and 30, 60, 120 and 180 minutes after the meal.

Results

T2D women had higher body mass index as well as higher femoral neck and total hip bone mineral density. At baseline, luteinizing hormone, follicle-stimulating hormone, osteocalcin and CTX levels were lower in group T2D. In response to the mixed meal, CTX and osteocalcin levels decreased and GLP-2 levels increased in both groups. The expected CTX suppression in response to the mixed meal was lower in group T2D.

Conclusions

Bone turnover markers were significantly reduced in T2D women at baseline. Confirming the role of nutrient intake as a stimulating factor, GLP-2 increased in response to the mixed meal in both groups. Importantly, CTX variation in response to the mixed meal was reduced in T2D women, suggesting abnormal response of bone remodeling to nutrient intake in T2D.

【 授权许可】

   
2015 Lopes et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Melton LJ 3rd, Leibson CL, Achenbach SJ, Therneau TM, Khosla S: Fracture risk in type 2 diabetes: update of a population-based study. J Bone Miner Res 2008, 23(8):1334-42.
• [2]Janghorbani M, Van Dam RM, Willett WC, Hu FB: Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007, 166(5):495-505.
• [3]Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T: Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 2009, 24(4):702-9.
• [4]de Liefde II, van der Klift M, de Laet CE, van Daele PL, Hofman A, Pols HA: Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporos Int 2005, 16(12):1713-20.
• [5]Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z, et al.: Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 2012, 27(5):319-32.
• [6]Moseley KF: Type 2 diabetes and bone fractures. Curr Opin Endocrinol Diabetes Obes 2012, 19(2):128-35.
• [7]Lee J, Vasikaran S: Current recommendations for laboratory testing and use of bone turnover markers in management of osteoporosis. Ann Lab Med 2012, 32(2):105-12.
• [8]Brown JP, Albert C, Nassar BA, Adachi JD, Cole D, Davison KS, et al.: Bone turnover markers in the management of postmenopausal osteoporosis. Clin Biochem 2009, 42(10–11):929-42.
• [9]Bjarnason NH, Henriksen EE, Alexandersen P, Christgau S, Henriksen DB, Christiansen C: Mechanism of circadian variation in bone resorption. Bone 2002, 30(1):307-13.
• [10]Walsh JS, Henriksen DB: Feeding and bone. Arch Biochem Biophys 2010, 503(1):11-9.
• [11]Clowes JA, Allen HC, Prentis DM, Eastell R, Blumsohn A: Octreotide abolishes the acute decrease in bone turnover in response to oral glucose. J Clin Endocrinol Metab 2003, 88(10):4867-73.
• [12]Henriksen DB, Alexandersen P, Bjarnason NH, Vilsboll T, Hartmann B, Henriksen EE, et al.: Role of gastrointestinal hormones in postprandial reduction of bone resorption. J Bone Miner Res 2003, 18(12):2180-9.
• [13]Pietschmann P, Resch H, Woloszczuk W, Willvonseder R: A circadian rhythm of serum osteocalcin levels in postmenopausal osteoporosis. Eur J Clin Invest 1990, 20(3):310-2.
• [14]Gottschalck IB, Jeppesen PB, Hartmann B, Holst JJ, Henriksen DB: Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and short-bowel syndrome. Scand J Gastroenterol 2008, 43(11):1304-10.
• [15]Ducy P: The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia 2011, 54(6):1291-7.
• [16]Yazbeck R, Howarth GS, Abbott CA: Growth factor based therapies and intestinal disease: is glucagon-like peptide-2 the new way forward? Cytokine Growth Factor Rev 2009, 20(2):175-84.
• [17]Drucker DJ: Glucagon-like peptide 2. J Clin Endocrinol Metab 2001, 86(4):1759-64.
• [18]Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, et al.: Four-month treatment with GLP-2 significantly increases hip BMD: a randomized, placebo-controlled, dose-ranging study in postmenopausal women with low BMD. Bone 2009, 45(5):833-42.
• [19]Holst JJ, Hartmann B, Gottschalck IB, Jeppesen PB, Miholic J, Henriksen DB: Bone resorption is decreased postprandially by intestinal factors and glucagon-like peptide-2 is a possible candidate. Scand J Gastroenterol 2007, 42(7):814-20.
• [20]Henriksen DB, Alexandersen P, Hartmann B, Adrian CL, Byrjalsen I, Bone HG, et al.: Disassociation of bone resorption and formation by GLP-2: a 14-day study in healthy postmenopausal women. Bone 2007, 40(3):723-9.
• [21]World Health Organization: Scientific Group on the assessment of osteoporosis at primary health care level (Internet). Brussels, Belgium: Summary Meeting Report. 2004. Avaiable from http://www.who.int/chp/topics/Osteoporosis.pdf.
• [22]American Diabetes Association: Diagnosis and classification of diabetes mellitus Diabetes Care 2010, 33(Suppl.1):S62-9.
• [23]Power MJ, O’Dwyer B, Breen E, Fottrell PF: Osteocalcin concentrations in plasma prepared with different anticoagulants. Clin Chem 1991, 37(2):281-4.
• [24]Lee AJ, Hodges S, Eastell R: Measurement of osteocalcin. Ann Clin Biochem 2000, 37(Pt 4):432-46.
• [25]Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C: Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab 1995, 80(3):864-8.
• [26]Valderas JP, Padilla O, Solari S, Escalona M, Gonzalez G: Feeding and bone turnover in gastric bypass. J Clin Endocrinol Metab 2014, 99(2):491-7.
• [27]Geloneze B, Lima MM, Pareja JC, Barreto MR, Magro DO: Association of insulin resistance and GLP-2 secretion in obesity: a pilot study. Arq Bras Endocrinol Metabol 2013, 57(8):632-5.
• [28]Kirkwood BR: Essential medical statistics. Blackwell Science, Massachusetts; 2006.
• [29]Chailurkit LO, Chanprasertyothin S, Rajatanavin R, Ongphiphadhanakul B: Reduced attenuation of bone resorption after oral glucose in type 2 diabetes. Clin Endocrinol (Oxf) 2008, 68(6):858-62.
• [30]Majima T, Komatsu Y, Yamada T, Koike Y, Shigemoto M, Takagi C, et al.: Decreased bone mineral density at the distal radius, but not at the lumbar spine or the femoral neck, in Japanese type 2 diabetic patients. Osteoporos Int 2005, 16(8):907-13.
• [31]Andersen S, Frederiksen KD, Hansen S, Brixen K, Gram J, Stoving RK: Bone structure and estimated bone strength in obese patients evaluated by high-resolution peripheral quantitative computed tomography. Calcif Tissue Int 2014, 95(1):19-28.
• [32]Codner E, Merino PM, Tena-Sempere M: Female reproduction and type 1 diabetes: from mechanisms to clinical findings. Hum Reprod Update 2012, 18(5):568-85.
• [33]Malacara JM, Huerta R, Rivera B, Esparza S, Fajardo ME: Menopause in normal and uncomplicated NIDT2D women: physical and emotional symptoms and hormone profile. Maturitas 1997, 28(1):35-45.
• [34]Isik S, Ozcan HN, Ozuguz U, Tutuncu YA, Berker D, Alimli AG, et al.: Evaluation of ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with type 2 diabetes mellitus. J Clin Endocrinol Metab 2012, 97(1):261-9.
• [35]Iqbal J, Blair HC, Zallone A, Sun L, Zaidi M: Further evidence that FSH causes bone loss independently of low estrogen. Endocrine 2012, 41(2):171-5.
• [36]Viljakainen H, Ivaska KK, Paldanius P, Lipsanen-Nyman M, Saukkonen T, Pietilainen KH, et al.: Suppressed bone turnover in obesity - a link to energy metabolism? A case–control study. J Clin Endocrinol Metab 2014, 99(6):2155-63.
• [37]Gottschalck IB, Jeppesen PB, Holst JJ, Henriksen DB: Reduction in bone resorption by exogenous glucagon-like peptide-2 administration requires an intact gastrointestinal tract. Scand J Gastroenterol 2008, 43(8):929-37.