Skip to main content
SpringerLink
Log in

Lifestyle Management of Diabetes: Implications for the Bone-Vascular Axis

  • Lifestyle Management to Reduce Diabetes/Cardiovascular Risk (B Conway and H Keenan, Section Editors)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To describe the main pathways involved in the interplay between bone and cardiovascular disease and to highlight the possible impact of physical activity and medical nutrition therapy on the bone-vascular axis.

Recent Findings

Diabetes increases the risk of both cardiovascular disease and bone fragility fractures, sharing common pathogenic pathways, including OPG/RANK/RANKL, the FGF23/Klotho axis, calciotropic hormones, and circulating osteogenic cells. This may offer new therapeutic targets for future treatment strategies. As lifestyle intervention is the cornerstone of diabetes treatment, there is potential for an impact on the bone-vascular axis.

Summary

Evidence published suggests the bone-vascular axis encompasses key pathways for cardiovascular disease. This, along with studies showing physical activity plays a crucial role in the prevention of both bone fragility and cardiovascular disease, suggests that lifestyle intervention incorporating exercise and diet may be helpful in managing skeletal health decline in diabetes. Studies investigating the controversial role of high-fiber diet and dietary vitamin D/calcium on bone and cardiovascular health suggest an overall benefit, but further investigations are needed in this regard.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. International Diabetes Federation. IDF Diabete Atlas. 8th ed. Brussel, Belgium: Internatio; 2017.

    Google Scholar 

  2. Rask-Madsen C, King GL. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab. Elsevier Inc. 2013;17:20–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. •• Lampropoulos CE, Papaioannou I, D’Cruz DP. Osteoporosis—a risk factor for cardiovascular disease? Nat Rev Rheumatol. 2012;8:587–98. This is a comprehensive review of the literature reporting the actual knowledge about the molecular pathways involved in the bone-vascular axis and summarizing the clinical evidences linking vascular calcification and osteoporosis.

    Article  CAS  PubMed  Google Scholar 

  4. Sprini D, Rini GB, Di Stefano L, Cianferotti L, Napoli N. Correlation between osteoporosis and cardiovascular disease. Clin Cases Miner Bone Metab. 2014;1:117–9.

    Google Scholar 

  5. Pedone C, Scarlata S, Napoli N, Lauretani F, Bandinelli S, Ferrucci L, et al. Relationship between bone cross-sectional area and indices of peripheral artery disease. Calcif Tissue Int. 2013;93(6):508–16. https://doi.org/10.1007/s00223-013-9782-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kiel DP, Kauppila LI, Cupples LA, Hannan MT, O’Donnell CJ, Wilson PW. Bone loss and the progression of abdominal aortic calcification over a 25 year period: the Framingham heart study. Calcif Tissue Int. 2001;68:271–6.

    Article  CAS  PubMed  Google Scholar 

  7. Sennerby U, Farahmand B, Ahlbom A, Ljunghall S, Michaëlsson K. Cardiovascular diseases and future risk of hip fracture in women. Osteoporos Int. 2007;18:1355–62.

    Article  CAS  PubMed  Google Scholar 

  8. Bagger YZ, Tankó LB, Alexandersen P, Qin G, Christiansen C. Radiographic measure of aorta calcification is a site-specific predictor of bone loss and fracture risk at the hip. J Intern Med. 2006;259:598–605.

    Article  CAS  PubMed  Google Scholar 

  9. 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;166:495–505.

    Article  PubMed  Google Scholar 

  10. Napoli N, Strotmeyer ES, Ensrud KE, Sellmeyer DE, Bauer DC, Hoffman AR, et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia. 2014;57:2057–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. • Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL, et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017;13:208–19. A comprehensive review of the literature about the pathophysiology of bone fragility as a complication of diabetes mellitus. Clinical data are summarized as well.

    Article  CAS  PubMed  Google Scholar 

  12. Maddaloni E, Cavallari I, Napoli N, Conte C. Vitamin D and diabetes mellitus. Front Horm Res. 2018;50:161–176

  13. Aguirre L, Napoli N, Waters D, Qualls C, Villareal DT, Armamento-Villareal R. Increasing adiposity is associated with higher adipokine levels and lower bone mineral density in obese older adults. J Clin Endocrinol Metab. 2014;99(9):3290–7. https://doi.org/10.1210/jc.2013-3200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Napoli N, Pedone C, Pozzilli P, Lauretani F, Bandinelli S, Ferrucci L, et al. Effect of ghrelin on bone mass density: the InChianti study. Bone. 2011;49(2):257–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142:296–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rosen CJ, Motyl KJ. No bones about it: insulin modulates skeletal remodeling. Cell. 2010;142:198–200.

    Article  CAS  PubMed  Google Scholar 

  17. Maddaloni E, D’Onofrio L, Lauria A, Maurizi AR, Strollo R, Palermo A, et al. Osteocalcin levels are inversely associated with Hba1c and BMI in adult subjects with long-standing type 1 diabetes. J Endocrinol Investig. 2014;37:661–6.

    Article  CAS  Google Scholar 

  18. Ducy P. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia. 2011;54:1291–7.

    Article  CAS  PubMed  Google Scholar 

  19. Booth SL, Centi A, Smith SR, Gundberg C. The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol. 2012;9:43–55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Oei L, Zillikens MC, Dehghan A, Buitendijk GHS, Castaño-Betancourt MC, Estrada K, et al. High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam study. Diabetes Care. 2013;36:1619–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Botolin S, McCabe LR. Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem. 2006;99:411–24.

    Article  CAS  PubMed  Google Scholar 

  22. McCabe LR. Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem. 2007;102:1343–57.

    Article  CAS  PubMed  Google Scholar 

  23. Maddaloni E, D’Eon S, Hastings S, Tinsley LJLJ, Napoli N, Khamaisi M, et al. Bone health in subjects with type 1 diabetes for more than 50 years. Acta Diabetol Springer Milan. 2017;54:1–10.

    Article  Google Scholar 

  24. Keenan HA, Maddaloni E. Bone microarchitecture in type 1 diabetes: it is complicated. Curr Osteoporos Rep. 2016;14:351–8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Miao J, Brismar K, Nyrén O, Ugarph-Morawski A, Ye W. Elevated hip fracture risk in type 1 diabetic patients: a population-based cohort study in Sweden. Diabetes Care. 2005;28:2850–5.

    Article  PubMed  Google Scholar 

  26. Maddaloni E, Pozzilli P. SMART diabetes: the way to go (safe and multifactorial approach to reduce the risk for therapy in diabetes). Endocrine. 2014;46:3–5.

    Article  CAS  PubMed  Google Scholar 

  27. Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation clinical expert consensus task force (ACCF/AHA writing committee to update the 2000 expert consensus document on electron beam computed tomography). Circulation. 2007;115:402–26.

    Article  PubMed  Google Scholar 

  28. Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. Circulation. 2008;117:2938–48.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Fadini GP, Rattazzi M, Matsumoto T, Asahara T, Khosla S. Emerging role of circulating calcifying cells in the bone-vascular axis. Circulation. 2012;125:2772–81.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Eghbali-Fatourechi GZ, Lamsam J, Fraser D, Nagel D, Riggs BL, Khosla S. Circulating osteoblast-lineage cells in humans. N Engl J Med. 2005;352:1959–66.

    Article  CAS  PubMed  Google Scholar 

  31. Eghbali-Fatourechi GZ, Mödder UIL, Charatcharoenwitthaya N, Sanyal A, Undale AH, Clowes JA, et al. Characterization of circulating osteoblast lineage cells in humans. Bone. 2007;40:1370–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Collin J, Gössl M, Matsuo Y, Cilluffo RR, Flammer AJ, Loeffler D, et al. Osteogenic monocytes within the coronary circulation and their association with plaque vulnerability in patients with early atherosclerosis. Int J Cardiol. 2015;181:57–64.

    Article  PubMed  Google Scholar 

  33. Fadini GP, Albiero M, Menegazzo L, Boscaro E, Vigili de Kreutzenberg S, Agostini C, et al. Widespread increase in myeloid calcifying cells contributes to ectopic vascular calcification in type 2 diabetes. Circ Res. 2011;108:1112–21.

    Article  CAS  PubMed  Google Scholar 

  34. Maddaloni E, Xia Y, Park K, D’Eon S, Tinsley LJ, St-Louis R, et al. High density lipoprotein modulates osteocalcin expression in circulating monocytes: a potential protective mechanism for cardiovascular disease in type 1 diabetes. Cardiovasc Diabetol. 2017;16:116.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ashen MD, Blumenthal RS. Clinical practice. Low HDL cholesterol levels. N Engl J Med. 2005;353(12):1252–60.

    Article  CAS  PubMed  Google Scholar 

  36. King AC, Haskell WL, Young DR, Oka RK, Stefanick ML. Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation. 1995;91(10):2596–604.

    Article  CAS  PubMed  Google Scholar 

  37. Ostman C, Smart NA, Morcos D, Duller A, Ridley W, Jewiss D. The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis. Cardiovasc Diabetol. 2017;16(1):110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fikenzer K, Fikenzer S, Laufs U, Werner C. Effects of endurance training on serum lipids. Vasc Pharmacol. 2018;101:9–20.

    Article  CAS  Google Scholar 

  39. Szymczyk KH, Freeman TA, Adams CS, Srinivas V, Steinbeck MJ. Active caspase-3 is required for osteoclast differentiation. J Cell Physiol. 2006;209:836–44.

    Article  CAS  PubMed  Google Scholar 

  40. Zheng CM, Chu P, Wu CC, Ma WY, Hung KC, Hsu YH, et al. Association between increased serum osteoprotegerin levels and improvement in bone mineral density after parathyroidectomy in hemodialysis patients. Tohoku J Exp Med. 2012;226(1):19–27.

    Article  CAS  PubMed  Google Scholar 

  41. Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol. 2002;22:549–53.

    Article  CAS  PubMed  Google Scholar 

  42. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem. 1998;273:14363–7.

    Article  CAS  PubMed  Google Scholar 

  43. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 1998;12:1260–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bjerre M, Hilden J, Kastrup J, Skoog M, Hansen JF, Kolmos HJ, et al. Claricor trial group: osteoprotegerin independently predicts mortality in patients with stable coronary artery disease: the CLARICOR trial. Scand J Clin Lab Invest. 2014;74:657–64.

    Article  CAS  PubMed  Google Scholar 

  45. Nascimento MM, Hayashi SY, Riella MC, Lindholm B. Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease. Braz J Med Biol Res. 2014;47:995–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Evrard S, Delanaye P, Kamel S, Cristol JP, Cavalier E. Vascular calcification: from pathophysiology to biomarkers. Clin Chim Acta. 2015;438:401–14.

    Article  CAS  PubMed  Google Scholar 

  47. Razzaque MS. Fgf23-mediated regulation of systemic phosphate homeostasis: is klotho an essential player? Am J Physiol Ren Physiol. 2009;296:F470–6.

    Article  CAS  Google Scholar 

  48. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45–51.

    Article  CAS  PubMed  Google Scholar 

  49. Zoppellaro G, Faggin E, Puato M, Pauletto P, Rattazzi M. Fibroblast growth factor 23 and the bone-vascular axis: lessons learned from animal studies. Am J Kidney Dis. 2012;59:135–44.

    Article  CAS  PubMed  Google Scholar 

  50. Baum M, Schiavi S, Dwarakanath V, Quigley R. Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules. Kidney Int. 2005;68:1148–53.

    Article  CAS  PubMed  Google Scholar 

  51. Tuñón J, Fernández-Fernández B, Carda R, Pello AM, Cristóbal C, Tarín N, et al. Circulating fibroblast growth factor-23 plasma levels predict adverse cardiovascular outcomes in patients with diabetes mellitus with coronary artery disease. Diabetes Metab Res Rev. 2016;32(7):685–93. https://doi.org/10.1002/dmrr.2787.

    Article  CAS  PubMed  Google Scholar 

  52. Nakahara T, Kawai-Kowase K, Matsui H, Sunaga H, Utsugi T, Iso T, et al. Fibroblast growth factor 23 inhibits osteoblastic gene expression and induces osteoprotegerin in vascular smooth muscle cells. Atherosclerosis. 2016;253:102–10.

    Article  CAS  PubMed  Google Scholar 

  53. Holick MF. Sunlight and vitamin D: both good for cardiovascular health. J Gen Intern Med. 2002;17:733–5.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, et al. 1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Circulation. 2009;120:687–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Neuhouser ML, Wassertheil-Smoller S, Thomson C, Aragaki A, Anderson GL, Manson JAE, et al. Multivitamin use and risk of cancer and cardiovascular disease in the Women’s health initiative cohorts. Arch Intern Med. 2009;169:294–304.

    Article  PubMed  Google Scholar 

  56. Thompson B, Towler DA. Arterial calcification and bone physiology: role of the bone-vascular axis. Nat Rev Endocrinol. 2012;8(9):529–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. American Diabetes Association (ADA). Lifestyle management: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S38–50.

    Article  Google Scholar 

  58. Ried-Larsen M, MacDonald CS, Johansen MY, Hansen KB, Christensen R, Almdal TP, et al. Why prescribe exercise as therapy in type 2 diabetes? We have a pill for that! Diabetes Metab Res Rev. 2018;34(5):e2999. https://doi.org/10.1002/dmrr.2999. Review

    Article  PubMed  Google Scholar 

  59. Peters A. Laffel L, Colberg SR, Riddell MC. Physical activity: regulation of glucose metabolism, clinicial management strategies, and weight control. In: American Diabetes Association/JDRF Type 1 Diabetes Sourcebook. American Diabetes Association; 2013.

  60. Bouchonville M, Armamento-Villareal R, Shah K, Napoli N, Sinacore DR, Qualls C, et al. Weight loss, exercise or both and cardiometabolic risk factors in obese older adults: results of a randomized controlled trial. Int J Obes. 2014;38(3):423–31. https://doi.org/10.1038/ijo.2013.122.

    Article  CAS  Google Scholar 

  61. Napoli N, Shah K, Waters DL, Sinacore DR, Qualls C, Villareal DT. Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults. Am J Clin Nutr. 2014;100(1):189–98. https://doi.org/10.3945/ajcn.113.082883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. •• Colberg SR, Sigal RJ, Yardley JE, Riddell MC, et al. Physical activity/exercise and diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2016;39(11):2065–79. In this document the American Diabetes Association declares that physical activity is recommended in diabetic population in order to prevent both bone health impairment and CV disease

    Article  PubMed  PubMed Central  Google Scholar 

  63. Armamento-Villareal R, Sadler C, Napoli N, Shah K, Chode S, Sinacore DR, et al. Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J Bone Miner Res. 2012;27(5):1215–21. https://doi.org/10.1002/jbmr.1560.

    Article  CAS  PubMed  Google Scholar 

  64. Bergström I, Parini P, Gustafsson SA, Andersson G, Brinck J. Physical training increases osteoprotegerin in postmenopausal women. J Bone Miner Metab. 2012;30(2):202–7.

    Article  CAS  PubMed  Google Scholar 

  65. Wanner M, Richard A, Martin B, Linseisen J, Rohrmann S. Associations between objective and self-reported physical activity and vitamin D serum levels in the US population. Cancer Causes Control. 2015;26(6):881–91.

    Article  PubMed  Google Scholar 

  66. Li DJ, Fu H, Zhao T, Ni M, Shen FM. Exercise-stimulated FGF23 promotes exercise performance via controlling the excess reactive oxygen species production and enhancing mitochondrial function in skeletal muscle. Metabolism. 2016;65(5):747–56.

    Article  CAS  PubMed  Google Scholar 

  67. Saghiv MS, Sira DB, Goldhammer E, Sagiv M. The effects of aerobic and anaerobic exercises on circulating soluble-Klotho and IGF-I in young and elderly adults and in CAD patients. J Circ Biomark. 2017;28:6.

    Google Scholar 

  68. Marques EA, Mota J, Viana JL, Tuna D, Figueiredo P, Guimarães JT, et al. Response of bone mineral density, inflammatory cytokines, and biochemical bone markers to a 32-week combined loading exercise programme in older men and women. Arch Gerontol Geriatr. 2013;57(2):226–33.

    Article  CAS  PubMed  Google Scholar 

  69. •• Authors/Task Force Members, Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts): developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur J Prev Cardiol. 2016;23(11):NP1–NP96. In this document the European Society of Cardiology and the European Association for Cardiovascular Prevention & Rehabilitation declare that physical activity plays a key role in the prevention of cardiovascular events and should be practice at least 4–5 days per week.

    Article  Google Scholar 

  70. Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011;364(13):1218–29. https://doi.org/10.1056/NEJMoa1008234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Troy KL, Mancuso ME, Butler TA, Johnson JE. Exercise early and often: effects of physical activity and exercise on women’s bone health. Int J Environ Res Public Health. 2018;15(5):878.

    Article  PubMed Central  Google Scholar 

  72. Palermo A, D'Onofrio L, Buzzetti R, Manfrini S, Napoli N. Pathophysiology of bone fragility in patients with diabetes. Calcif Tissue Int. 2017;100(2):122–32.

    Article  CAS  PubMed  Google Scholar 

  73. Sanches CP, Vianna AGD, Barreto FC. The impact of type 2 diabetes on bone metabolism. Diabetol Metab Syndr. 2017;9:85.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Rossini M, Adami S, Bertoldo F, Diacinti D, Gatti D, (SIOMMS). Guidelines for the diagnosis, prevention and management of osteoporosis. Reumatismo. 2016;68(1):1–39.

    Article  CAS  PubMed  Google Scholar 

  75. Zhao R, Zhang M, Zhang Q. The effectiveness of combined exercise interventions for preventing postmenopausal bone loss: a systematic review and meta-analysis. J Orthop Sports Phys Ther. 2017;47:241–51.

    Article  PubMed  Google Scholar 

  76. Hordern MD, Dunstan DW, Prins JB, Baker MK. Exercise prescription for patients with type 2 diabetes and pre-diabetes: a position statement from exercise and sport science Australia. J Sci Med Sport. 2012;15(1):25–31.

    Article  PubMed  Google Scholar 

  77. Gomez-Cabello A, Ara I, González-Agüero A, Casajus JA, Vicente-Rodriguez G. Effects of training on bone mass in older adults: a systematic review. Sports Med. 2012;42:301–25.

    Article  CAS  PubMed  Google Scholar 

  78. Zhao R, Zhao M, Xu Z. The effects of differing resistance training modes on the preservation of bone mineral density in postmenopausal women: a meta-analysis. Osteoporos Int. 2015;26:1605–18.

    Article  CAS  PubMed  Google Scholar 

  79. Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012;9:CD007146.

    Google Scholar 

  80. De Kam D, Smulders E, Weerdesteyn V, Smits-Engelsman BCM. Exercise interventions to reduce fall-related fractures and their risk factors in individuals with low bone density: a systematic review of randomized controlled trials. Osteoporos Int. 2009;20:2111–25.

    Article  PubMed  Google Scholar 

  81. Boulé NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia. 2003;46(8):1071–81.

    Article  PubMed  Google Scholar 

  82. Otten J, Stomby A, Waling M, Isaksson A, Tellström A, Lundin-Olsson L, et al. Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes. Diabetes Metab Res Rev. 2017;33(1) https://doi.org/10.1002/dmrr.2828.

    Article  CAS  Google Scholar 

  83. Church T. Exercise in obesity, metabolic syndrome, and diabetes. Prog Cardiovasc Dis. 2011;53(6):412–8.

    Article  PubMed  Google Scholar 

  84. Cesari F, Sofi F, Gori AM, Corsani CA, Caporale R, Abbate R, et al. Physical activity and circulating endothelial progenitor cells: an intervention study. Eur J Clin Investig. 2012;42(9):927–32.

    Article  CAS  Google Scholar 

  85. Miele EM, Headley SAE. The effects of chronic aerobic exercise on cardiovascular risk factors in persons with diabetes mellitus. Curr Diab Rep. 2017;17(10):97. https://doi.org/10.1007/s11892-017-0927-7.

    Article  CAS  PubMed  Google Scholar 

  86. Pattyn N, Cornelissen VA, Eshghi SR, Vanhees L. The effect of exercise on the cardiovascular risk factors constituting the metabolic syndrome: a meta-analysis of controlled trials. Sports Med. 2013;43(2):121–33.

    Article  PubMed  Google Scholar 

  87. Kessler HS, Sisson SB, Short KR. The potential for high-intensity interval training to reduce cardiometabolic disease risk. Sports Med. 2012;42(6):489–509.

    Article  PubMed  Google Scholar 

  88. Fealy CE, Nieuwoudt S, Foucher JA, Scelsi AR, Malin SK, Pagadala M, et al. Functional high intensity exercise training ameliorates insulin resistance and cardiometabolic risk factors in type 2 diabetes. Exp Physiol. 2018;103:985–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Freese EC, Gist NH, Acitelli RM, McConnell WJ, Beck CD, et al. Acute and chronic effects of sprint interval exercise on postprandial lipemia in women at-risk for the metabolic syndrome. J Appl Physiol (1985). 2015;118(7):872–9.

    Article  Google Scholar 

  90. Lund J, Rustan AC, Løvsletten NG, Mudry JM, Langleite TM, Feng YZ, et al. Exercise in vivo marks human myotubes in vitro: training-induced increase in lipid metabolism. PLoS One. 2017;12(4):e0175441.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Trumbo P, Schlicker S, Yates AA, Poos M, Food and Nutrition Board of the Institute of Medicine, The National Academies. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. Food and Nutrition Board of the Institute of Medicine, The National Academies. J Am Diet Assoc. 2002;102(11):1621–30.

    Article  PubMed  Google Scholar 

  92. Dai Z, Zhang Y, Lu N, Felson DT, Kiel DP, Sahni S. Association between dietary Fiber intake and bone loss in the Framingham offspring study. J Bone Miner Res. 2018;33(2):241–9. https://doi.org/10.1002/jbmr.3308.

    Article  CAS  PubMed  Google Scholar 

  93. McCabe L, Britton RA, Parameswaran N. Prebiotic and probiotic regulation of bone health: role of the intestine and its microbiome. Curr Osteoporos Rep. 2015;13(6):363–71.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Amalraj A, Pius A. Bioavailability of calcium and its absorption inhibitors in raw and cooked green leafy vegetables commonly consumed in India—an in vitro study. Food Chem. 2015;170:430–6. https://doi.org/10.1016/j.foodchem.2014.08.031.

    Article  CAS  PubMed  Google Scholar 

  95. Shah M, Chandalia M, Adams-Huet B, Brinkley LJ, Sakhaee K, Grundy SM, et al. Effect of a high-fiber diet compared with a moderate-fiber diet on calcium and other mineral balances in subjects with type 2 diabetes. Diabetes Care. 2009;32(6):990–5. https://doi.org/10.2337/dc09-0126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Whisner CM, Martin BR, Nakatsu CH, Story JA, MacDonald-Clarke CJ, McCabe LD, et al. Soluble corn fiber increases calcium absorption associated with shifts in the gut microbiome: a randomized dose-response trial in free-living pubertal females. J Nutr. 2016;146(7):1298–306. https://doi.org/10.3945/jn.115.227256.

    Article  CAS  PubMed  Google Scholar 

  97. Jakeman SA, Henry CN, Martin BR, McCabe GP, McCabe LD, Jackson GS, et al. Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial. Am J Clin Nutr. 2016;104(3):837–43. https://doi.org/10.3945/ajcn.116.132761.

    Article  CAS  PubMed  Google Scholar 

  98. Bryk G, Coronel MZ, Pellegrini G, Mandalunis P, Rio ME, de Portela MLPM, et al. Effect of a combination GOS/FOS® prebiotic mixture and interaction with calcium intake on mineral absorption and bone parameters in growing rats. Eur J Nutr. 2015;54(6):913–23. https://doi.org/10.1007/s00394-014-0768-y.

    Article  CAS  PubMed  Google Scholar 

  99. •• Lucas S, et al. Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun. 2018;9(1):55. https://doi.org/10.1038/s41467-017-02490-4. In this study, the effect of high fiber diet, SCFAs administration and bacterial transfer on bone microarchitecture in vivo. Moreover, it shows how SCFAs can interfere with osteoclast differentiation toward the suppression of bone resorption.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Martin BR, Braun MM, Wigertz K, Bryant R, Zhao Y, Lee WH, et al. Fructo-oligosaccharides and calcium absorption and retention in adolescent girls. J Am Coll Nutr. 2010;29(4):382–6.

    Article  CAS  PubMed  Google Scholar 

  101. Kosk D, Kramer H, Luke A, Camacho P, Bovet P, Rhule JP, et al. Dietary factors and fibroblast growth factor-23 levels in young adults with African ancestry. J Bone Miner Metab. 2017;35(6):666–74. https://doi.org/10.1007/s00774-016-0804-5.

    Article  CAS  PubMed  Google Scholar 

  102. Grooms KN, et al. Dietary fiber intake and cardiometabolic risks among US adults, NHANES 1999–2010. Am J Med. 2013;126(12):1059–67.e1–4. https://doi.org/10.1016/j.amjmed.2013.07.023.

    Article  CAS  PubMed  Google Scholar 

  103. Threapleton DE, Greenwood DC, Evans CEL, Cleghorn CL, Nykjaer C, Woodhead C, et al. Dietary fiber intake and risk of cardiovascular disease systematic review and meta-analysis. BMJ. 2013;347:f6879. https://doi.org/10.1136/bmj.f6879.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Kim Y, Je Y. Dietary fiber intake and mortality from cardiovascular disease and all cancers: a meta-analysis of prospective cohort studies. Arch Cardiovasc Dis. 2016;109(1):39–54. https://doi.org/10.1016/j.acvd.2015.09.005.

    Article  PubMed  Google Scholar 

  105. Chan CW, Lee PH. Association between dietary fiber intake with cancer and all-cause mortality among 15 740 adults: the National Health and Nutrition Examination Survey III. J Hum Nutr Diet. 2016;29(5):633–42. https://doi.org/10.1111/jhn.12389.

    Article  CAS  PubMed  Google Scholar 

  106. Veronese N, Solmi M, Caruso MG, Giannelli G, Osella AR, Evangelou E, et al. Dietary fiber and health outcomes: an umbrella review of systematic reviews and meta-analyses. Am J Clin Nutr. 2018;107(3):436–44. https://doi.org/10.1093/ajcn/nqx082.

    Article  PubMed  Google Scholar 

  107. Mirmiran P, Bahadoran Z, Khalili Moghadam S, Zadeh Vakili A, Azizi F. A prospective study of different types of dietary fiber and risk of cardiovascular disease: Tehran lipid and glucose study. Nutrients. 2016;8(11):686. https://doi.org/10.3390/nu8110686.

    Article  CAS  PubMed Central  Google Scholar 

  108. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999;69(1):30–42.

    Article  CAS  PubMed  Google Scholar 

  109. Zhu X, Tu Y, Chen H, Jackson AO, Patel V, Yin K. Micro-environment and intracellular metabolism modulation of adipose tissue macrophage polarization in relation to chronic inflammatory diseases. Diabetes Metab Res Rev. 2018;34(5):e2993. https://doi.org/10.1002/dmrr.2993. Review

    Article  CAS  PubMed  Google Scholar 

  110. Vitale M, Masulli M, Cocozza S, Anichini R, Babini AC, Boemi M, et al. Sex differences in food choices, adherence to dietary recommendations and plasma lipid profile in type 2 diabetes—the TOSCA.IT study. Nutr Metab Cardiovasc Dis. 2016;26(10):879–85. https://doi.org/10.1016/j.numecd.2016.04.006.

    Article  CAS  PubMed  Google Scholar 

  111. Chandalia M, Garg A, Lutjohann D, von Bergmann K, Grundy SM, Brinkley LJ. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. N Engl J Med. 2000;342:1392–8. https://doi.org/10.1056/NEJM200005113421903.

    Article  CAS  PubMed  Google Scholar 

  112. Cesareo R, Iozzino M, D’onofrio L, Terrinoni I, Maddaloni E, Casini A, et al. Effectiveness and safety of calcium and vitamin D treatment for postmenopausal osteoporosis. Minerva Endocrinol. 2015;40(3):231–7

  113. The National Osteoporosis Foundation (NOF). Clinician’s guide to prevention and treatment of osteoporosis 2014. Osteoporos Int. 2014;25(10):2359–81. https://doi.org/10.1007/s00198-014-2794-2.

    Article  Google Scholar 

  114. Institute of Medicine (US) Committee to review dietary reference intakes for vitamin D and calcium. In: Ross AC, Taylor CL, Yaktine AL et al (eds) Dietary reference intakes for calcium and vitamin D. National Academies Press (US), Washington (DC); 2011.

  115. Xiong J, et al. Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone. 2014;66:146–54. https://doi.org/10.1016/j.bone.2014.06.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Feng Y, Zhou M, Zhang Q, Liu H, Xu Y, Shu L, et al. Synergistic effects of high dietary calcium and exogenous parathyroid hormone in promoting osteoblastic bone formation in mice. Br J Nutr. 2015;113(6):909–22. https://doi.org/10.1017/S0007114514004309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Anderson PH, Sawyer RK, Moore AJ, May BK, O’Loughlin PD, Morris HA. Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res. 2008;23(11):1789–97.

    Article  CAS  PubMed  Google Scholar 

  118. Kosk D, Kramer H, Luke A, Camacho P, Bovet P, Rhule JP, et al. Dietary factors and fibroblast growth factor-23 levels in young adults with African ancestry. J Bone Miner Metab. 2017;35(6):666–74. https://doi.org/10.1007/s00774-016-0804-5.

    Article  CAS  PubMed  Google Scholar 

  119. Di Giuseppe R, Kuhn T, Hirche F, Buijsse B, Dierkes J, Fritsche A, et al. Potential predictors of plasma fibroblast growth factor 23 concentrations: cross-sectional analysis in the EPIC-Germany study. PLoS One. 2015;10:e0133580.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. USDA and US Department of Health and Human Services. Dietary guidelines for Americans, 2015–2020. 8th ed. Washington (DC): US Government Printing Office; 2015.

    Google Scholar 

  121. Sahni S, Mangano KM, Tucker KL, Kiel DP, Casey VA, Hannan MT. Protective association of milk intake on the risk of hip fracture: results from the Framingham original cohort. J Bone Miner Res. 2014;29(8):1756–62. https://doi.org/10.1002/jbmr.2219.

    Article  CAS  PubMed  Google Scholar 

  122. van Dongen LH, Kiel DP, Soedamah-Muthu SS, Bouxsein ML, Hannan MT, Sahni S. Higher dairy food intake is associated with higher spine quantitative computed tomography (QCT) bone measures in the Framingham study for men but not women. J Bone Miner Res. 2018;33:1283–90. https://doi.org/10.1002/jbmr.3414.

    Article  CAS  PubMed  Google Scholar 

  123. Radavelli-Bagatini S, Zhu K, Lewis JR, Prince RL. Dairy food intake, peripheral bone structure, and muscle mass in elderly ambulatory women. J Bone Miner Res. 2014;29(7):1691–700. https://doi.org/10.1002/jbmr.2181.

    Article  CAS  PubMed  Google Scholar 

  124. Sahni S, Mangano KM, Kiel DP, Tucker KL, Hannan MT. Dairy intake is protective against bone loss in older vitamin D supplement users: the Framingham study. J Nutr. 2017;147(4):645–52. https://doi.org/10.3945/jn.116.240390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Michaëlsson K, et al. Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ. 2014;349:g6015. https://doi.org/10.1136/bmj.g6015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Bian S, Hu J, Zhang K, Wang Y, Yu M, Ma J. Dairy product consumption and risk of hip fracture: a systematic review and meta-analysis. BMC Public Health. 2018;18(1):165. https://doi.org/10.1186/s12889-018-5041-5.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Feskanich D, Bischoff-Ferrari HA, Frazier AL, Willett WC. Milk consumption during teenage years and risk of hip fractures in older adults. JAMA Pediatr. 2014;168(1):54–60. https://doi.org/10.1001/jamapediatrics.2013.3821.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Wadolowska L, Sobas K, Szczepanska J, Slowinska M, Czlapka-Matyasik M, Niedzwiedzka E. Dairy products, dietary calcium and bone health: possibility of prevention of osteoporosis in women: the Polish experience. Nutrients. 2013;5(7):2684–707. https://doi.org/10.3390/nu5072684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. • Biver, et al. Fermented dairy products consumption is associated with attenuated cortical bone loss independently of total calcium, protein, and energy intakes in healthy postmenopausal women. Osteoporos Int. 2018. https://doi.org/10.1007/s00198-018-4535-4. In this study, the evolution of bone microarchitecture, strength and structure in relation to dairies consumption are investigated in parallel with differences in biological markers such as CTX, PTH and Vitamin D.

    Article  CAS  PubMed  Google Scholar 

  130. Rizzoli R, Biver E. Effects of fermented milk products on bone. Calcif Tissue Int. 2018;102(4):489–500.

    Article  CAS  PubMed  Google Scholar 

  131. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035. https://doi.org/10.1136/bmj.g2035.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Fry CM, Sanders TA. Vitamin D and risk of CVD: a review of the evidence. Proc Nutr Soc. 2015;74(3):245–57. https://doi.org/10.1017/S0029665115000014.

    Article  CAS  PubMed  Google Scholar 

  133. Censani M, et al. Vitamin D deficiency associated with markers of cardiovascular disease in children with obesity. Glob Pediatr Health. 2018;5:2333794X17751773. https://doi.org/10.1177/2333794X17751773.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Wang Y, Si S, Liu J, Wang Z, Jia H, Feng K, et al. The associations of serum lipids with vitamin D status. PLoS One. 2016;11(10):e0165157. https://doi.org/10.1371/journal.pone.0165157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Schmidt N, Brandsch C, Kühne H, Thiele A, Hirche F, Stangl GI. Vitamin D receptor deficiency and low vitamin D diet stimulate aortic calcification and osteogenic key factor expression in mice. PLoS One. 2012;7(4):e35316. https://doi.org/10.1371/journal.pone.0035316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Kubiak JM. Vitamin D supplementation does not improve CVD risk factors in vitamin D insufficient subjects. Endocr Connect. 2018. https://doi.org/10.1530/EC-18-0144.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Anderson JJB, Klemmer PJ. Risk of high dietary calcium for arterial calcification in older adults. Nutrients. 2013;5(10):3964–74. https://doi.org/10.3390/nu5103964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Reid IR. Cardiovascular effects of calcium supplements. Nutrients. 2013;5(7):2522–9. https://doi.org/10.3390/nu5072522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Yang B, Campbell PT, Gapstur SM, Jacobs EJ, Bostick RM, Fedirko V, et al. Calcium intake and mortality from all causes, cancer, and cardiovascular disease: the cancer prevention study II nutrition cohort. Am J Clin Nutr. 2016;103(3):886–94. https://doi.org/10.3945/ajcn.115.117994.

    Article  CAS  PubMed  Google Scholar 

  140. Kong SH, Kim JH, Hong AR, Cho NH, Shin CS. Dietary calcium intake and risk of cardiovascular disease, stroke, and fracture in a population with low calcium intake. Am J Clin Nutr. 2017;106(1):27–34. https://doi.org/10.3945/ajcn.116.148171.

    Article  CAS  PubMed  Google Scholar 

  141. Khan B, Nowson CA, Daly RM, English DR, Hodge AM, Giles GG, et al. Higher dietary calcium intakes are associated with reduced risks of fractures, cardiovascular events, and mortality: a prospective cohort study of older men and women. J Bone Miner Res. 2015;30(10):1758–66. https://doi.org/10.1002/jbmr.2515.

    Article  CAS  PubMed  Google Scholar 

  142. Anderson JJ. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the multi-ethnic study of atherosclerosis (MESA). J Am Heart Assoc. 2016;5(10):e003815.

    Article  PubMed  PubMed Central  Google Scholar 

  143. •• Kopecky SL, et al. Lack of evidence linking calcium with or without vitamin D supplementation to cardiovascular disease in generally healthy adults: a clinical guideline from the National Osteoporosis Foundation and the American Society for Preventive Cardiology. Ann Intern Med. 2016;165(12):867–8. https://doi.org/10.7326/M16-1743. In this document the National Osteoporosis Foundation and the American Society for Preventive Cardiology declare that calcium intake from food or supplements has no relationship to the risk for cardiovascular disease, mortality, or all-cause mortality in generally healthy adults.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128, Rome, Italy

    Silvia Pieralice, Francesca Vigevano, Rossella Del Toro, Nicola Napoli & Ernesto Maddaloni

Authors
  1. Silvia Pieralice
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Vigevano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rossella Del Toro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicola Napoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ernesto Maddaloni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ernesto Maddaloni.

Ethics declarations

Conflict of Interest

Ernesto Maddaloni has received speaker fees from Merck-Serono and grant support from scientific societies with support from AstraZeneca and Lilly.

Silvia Pieralice, Francesca Vigevano, Rossella Del Toro, and Nicola Napoli declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Additional information

This article is part of the Topical Collection on Lifestyle Management to Reduce Diabetes/Cardiovascular Risk

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pieralice, S., Vigevano, F., Del Toro, R. et al. Lifestyle Management of Diabetes: Implications for the Bone-Vascular Axis. Curr Diab Rep 18, 84 (2018). https://doi.org/10.1007/s11892-018-1060-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11892-018-1060-y

Keywords

Search

Navigation