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Visit-to-visit variation of fasting plasma glucose is a predictor of hip fracture in older persons with type 2 diabetes: the Taiwan Diabetes Study

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Abstract

Summary

We investigated the association between fasting plasma glucose variability (FPG-CV) and the risk of hip fracture in elderly diabetic patients. Our finding showed a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures.

Introduction

Hip fracture is a major health burden in the population and is associated with high rates of mortality and morbidity especially in elderly. It is evident that diabetes mellitus is a risk factor of osteoporosis which is a significant risk factor of hip fracture. However, epidemiological studies exploring the risks of hip fracture among type 2 diabetic patients are limited.

Methods

A retrospective study of 26,501 ethnic Chinese older persons enrolled in the National Diabetes Care Management program in Taiwan was conducted; related factors were analyzed with extended Cox proportional hazards regression models to competing risk data on hip fracture incidence.

Results

The results show a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures, confirming a linear relationship between the two. After multivariate adjustment, the risk of hip fracture increased among patients with FPG-CV of 25.4–42.3 % and >42.3 % compared with patients with FPG-CV of ≦ 14.3 % (hazard ratio, 1.35; 95 % confidence interval 1.14–1.60 and 1.27; 1.07–1.52, respectively). Significant linear trends among various FPG-CV were observed.

Conclusions

Thus, the present study demonstrated the importance of glucose stability for fracture prevention in older persons with type 2 diabetes. Future studies should be conducted to explore whether reduction in glucose oscillation in older adults with diabetes mellitus can reduce the risk of hip fracture.

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Abbreviations

CV:

Coefficient of variation

FPG:

Fasting plasma glucose

NDCMP:

National Diabetes Care Management Program

ICD-9- CM:

International Classification of Disease, 9th Revision, Clinical Modification

NHI:

National Health Insurance

PIN:

Personal identification number

NHIRD:

National Health Insurance Research Database

DKA:

Ketoacidosis

HHNK:

Hyperglycemic hyperosmolar nonketotic coma

HRs:

Hazard ratios

CIs:

Confidence intervals

OAD:

Oral glucose-lowering drug

P1NP:

Procollagen type 1 amino-terminal propeptide

CTX-I:

C-terminal telopeptide of type I collagen

IFG:

Impaired fasting glucose

IGT:

Impaired glucose tolerance.

References

  1. Strom O, Borgstrom F, Kanis JA, Compston J, Cooper C, McCloskey EV, Jonsson B (2011) Osteoporosis: burden, health care provision and opportunities in the EU: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 6:59–155

    Article  CAS  PubMed  Google Scholar 

  2. Robbins J, Aragaki AK, Kooperberg C et al (2007) Factors associated with 5-year risk of hip fracture in postmenopausal women. Jama 298:2389–2398

    Article  CAS  PubMed  Google Scholar 

  3. Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B, Oglesby AK (2003) The components of excess mortality after hip fracture. Bone 32:468–473

    Article  CAS  PubMed  Google Scholar 

  4. Janghorbani M, Feskanich D, Willett WC, Hu F (2006) Prospective study of diabetes and risk of hip fracture: the Nurses’ Health Study. Diabetes Care 29:1573–1578

    Article  PubMed  Google Scholar 

  5. Fan Y, Wei F, Lang Y, Liu Y (2016) Diabetes mellitus and risk of hip fractures: a meta-analysis. Osteoporosis Int J Established Result Cooperation Between Eur Found Osteoporosis Nation Osteoporosis Found USA 27:219–228

    Article  CAS  Google Scholar 

  6. Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z, Yu Q, Zillikens MC, Gao X, Rivadeneira F (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27:319–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ceriello A, Ihnat MA (2010) ’Glycaemic variability’: a new therapeutic challenge in diabetes and the critical care setting. Diabetic Med J British Diabetic Assoc 27:862–867

    Article  CAS  Google Scholar 

  8. Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D (2008) Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57:1349–1354

    Article  CAS  PubMed  Google Scholar 

  9. Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A (2003) Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 52:2795–2804

    Article  CAS  PubMed  Google Scholar 

  10. Ihnat MAKR, Thorpe JE, Green DE, Kamat CD (2007) Attenuated superoxide dismutase induction in retinal cells in response to intermittent high versus continuous high glucose. Am J Biochem Biotechol 3:16–23

    Article  CAS  Google Scholar 

  11. Wu VC, Huang TM, Wu PC et al (2012) Preoperative proteinuria is associated with long-term progression to chronic dialysis and mortality after coronary artery bypass grafting surgery. PLoS One 7:e27687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 12. National Health Insurance Administration MoHaW (2010) The National Health Insurance Statistics, 2010. http://www.nhi.gov.tw/English/webdata/webdata.aspx?menu=11&menu_id=296&WD_ID=296&webdata_id=4010

  13. Kilpatrick ES, Rigby AS, Atkin SL (2008) A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care 31:2198–2202

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lunn M, McNeil D (1995) Applying Cox regression to competing risks. Biometrics 51:524–532

    Article  CAS  PubMed  Google Scholar 

  15. Nalysnyk L, Hernandez-Medina M, Krishnarajah G (2010) Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature. Diabetes Obes Metab 12:288–298

    Article  CAS  PubMed  Google Scholar 

  16. Lin CC, Li CI, Yang SY, Liu CS, Chen CC, Fuh MM, Chen W, Li TC (2012) Variation of fasting plasma glucose: a predictor of mortality in patients with type 2 diabetes. Am J Med 125(416):e419–418

    Google Scholar 

  17. Lin CC, Yang CP, Li CI, Liu CS, Chen CC, Lin WY, Hwang KL, Yang SY, Li TC (2014) Visit-to-visit variability of fasting plasma glucose as predictor of ischemic stroke: competing risk analysis in a national cohort of Taiwan Diabetes Study. BMC Med 12:165

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cheng D, Fei Y, Liu Y, Li J, Xue Q, Wang X, Wang N (2014) HbA1C variability and the risk of renal status progression in Diabetes Mellitus: a meta-analysis. PLoS One 9:e115509

    Article  PubMed  PubMed Central  Google Scholar 

  19. Puar TH, Khoo JJ, Cho LW, Xu Y, Chen YT, Chuo AM, Poh CB, Ng JM (2012) Association between glycemic control and hip fracture. J Am Geriatr Soc 60:1493–1497

    Article  PubMed  Google Scholar 

  20. Schwartz AV, Margolis KL, Sellmeyer DE et al (2012) Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial. Diabetes Care 35:1525–1531

    Article  PubMed  PubMed Central  Google Scholar 

  21. Schneider AL, Williams EK, Brancati FL, Blecker S, Coresh J, Selvin E (2013) Diabetes and risk of fracture-related hospitalization: the Atherosclerosis Risk in Communities Study. Diabetes Care 36:1153–1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Oei L, Zillikens MC, Dehghan A et al (2013) High bone mineral density and fracture risk in type 2 diabetes as skeletal complications of inadequate glucose control: the Rotterdam Study. Diabetes Care 36:1619–1628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shu A, Yin MT, Stein E, Cremers S, Dworakowski E, Ives R, Rubin MR (2012) Bone structure and turnover in type 2 diabetes mellitus. Osteoporosis Int J Established Result Cooperation Between Eur Foundation Osteoporosis and National Osteoporosis Found USA 23:635–641

    Article  CAS  Google Scholar 

  24. Dobnig H, Piswanger-Solkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Sieberer C, Fahrleitner-Pammer A (2006) Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 91:3355–3363

    Article  CAS  PubMed  Google Scholar 

  25. Alikhani M, Alikhani Z, Boyd C, MacLellan CM, Raptis M, Liu R, Pischon N, Trackman PC, Gerstenfeld L, Graves DT (2007) Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 40:345–353

    Article  CAS  PubMed  Google Scholar 

  26. Paul RG, Bailey AJ (1996) Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol 28:1297–1310

    Article  CAS  PubMed  Google Scholar 

  27. Vashishth D, Gibson GJ, Khoury JI, Schaffler MB, Kimura J, Fyhrie DP (2001) Influence of nonenzymatic glycation on biomechanical properties of cortical bone. Bone 28:195–201

    Article  CAS  PubMed  Google Scholar 

  28. Chailurkit LO, Chanprasertyothin S, Rajatanavin R, Ongphiphadhanakul B (2008) Reduced attenuation of bone resorption after oral glucose in type 2 diabetes. Clin Endocrinol 68:858–862

    Article  CAS  Google Scholar 

  29. Li CI, Liu CS, Lin WY, Meng NH, Chen CC, Yang SY, Chen HJ, Lin CC, Li TC (2015) Glycated hemoglobin level and risk of hip fracture in older people with type 2 diabetes: a competing risk analysis of Taiwan Diabetes Cohort Study. J Bone Mineral Res Off J Am Soc Bone Mineral Res 30:1338–1346

    Article  CAS  Google Scholar 

  30. Garcia-Hernandez A, Arzate H, Gil-Chavarria I, Rojo R, Moreno-Fierros L (2012) High glucose concentrations alter the biomineralization process in human osteoblastic cells. Bone 50:276–288

    Article  CAS  PubMed  Google Scholar 

  31. De L II, Van Der Klift M, De Laet CE, Van Daele PL, Hofman A, Pols HA (2005) Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. Osteoporosis international. J Established Result Cooperation Between Eur Found Osteoporosis Nation Osteoporosis Found USA 16:1713–1720

    Article  Google Scholar 

  32. Christiansen C, Christensen MS, McNair P, Nielsen B, Madsbad S (1982) Vitamin D metabolites in diabetic patients: decreased serum concentration of 24,25-dihydroxyvitamin D. Scand J Clin Lab Invest 42:487–491

    Article  CAS  PubMed  Google Scholar 

  33. Nyomba BL, Verhaeghe J, Thomasset M, Lissens W, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. I. Abnormal vitamin D metabolism and impaired active intestinal calcium absorption. Endocrinology 124:565–572

    Article  CAS  PubMed  Google Scholar 

  34. Balint E, Szabo P, Marshall CF, Sprague SM (2001) Glucose-induced inhibition of in vitro bone mineralization. Bone 28:21–28

    Article  CAS  PubMed  Google Scholar 

  35. Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501

    Article  CAS  PubMed  Google Scholar 

  36. Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner PJ, Jamal SA, Black DM, Cummings SR (2001) Study of Osteoporotic Features Research G (2001) Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 86:32–38

    Article  CAS  PubMed  Google Scholar 

  37. Ivers RQ, Cumming RG, Mitchell P, Peduto AJ, Blue Mountains Eye S (2001) Diabetes and risk of fracture: The Blue Mountains Eye Study. Diabetes Care 24:1198–1203

    Article  CAS  PubMed  Google Scholar 

  38. Roman de Mettelinge T, Cambier D, Calders P, Van Den Noortgate N, Delbaere K (2013) Understanding the relationship between type 2 diabetes mellitus and falls in older adults: a prospective cohort study. PLoS One 8:e67055

    Article  PubMed  PubMed Central  Google Scholar 

  39. Macgilchrist C, Paul L, Ellis BM, Howe TE, Kennon B, Godwin J (2010) Lower-limb risk factors for falls in people with diabetes mellitus. Diabet Med 27:162–168

    Article  CAS  PubMed  Google Scholar 

  40. Pijpers E, Ferreira I, de Jongh RT, Deeg DJ, Lips P, Stehouwer CD, Nieuwenhuijzen Kruseman AC (2012) Older individuals with diabetes have an increased risk of recurrent falls: analysis of potential mediating factors: the Longitudinal Ageing Study Amsterdam. Age Ageing 41:358–365

    Article  PubMed  Google Scholar 

  41. de Waard EA, van Geel TA, Savelberg HH, Koster A, Geusens PP, van den Bergh JP (2014) Increased fracture risk in patients with type 2 diabetes mellitus: an overview of the underlying mechanisms and the usefulness of imaging modalities and fracture risk assessment tools. Maturitas 79:265–274

    Article  PubMed  Google Scholar 

  42. Callaly EL, Ni Chroinin D, Hannon N et al (2015) Falls and fractures 2 years after acute stroke: the North Dublin Population Stroke Study. Age Ageing 44:882–886

    Article  CAS  PubMed  Google Scholar 

  43. Ceriello A, Novials A, Ortega E, La Sala L, Pujadas G, Testa R, Bonfigli AR, Esposito K, Giugliano D (2012) Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. Diabetes 61:2993–2997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Mody N, Parhami F, Sarafian TA, Demer LL (2001) Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 31:509–519

    Article  CAS  PubMed  Google Scholar 

  45. Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR (1990) Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 85:632–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Basu S, Michaelsson K, Olofsson H, Johansson S, Melhus H (2001) Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun 288:275–279

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was funded primarily by the Bureau of National Health Insurance (DOH94-NH-1007), the Ministry of Science and Technology of Taiwan (NSC 101-2314-B-039 -017-MY3 & NSC 102-2314-B-039-005-MY2 & MOST 104-2314-B-039-016), and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019) and China Medical University Hospital (DMR-104-087).

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Correspondence to C.-C. Lin.

Ethics declarations

This study was approved by the Ethical Review Board of China Medical University Hospital (CMUH103-REC2-156).

Conflicts of interest

None.

Additional information

Tsai-Chung Li equally contributed as first author.

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Chiang, J.IH., Li, TC., Li, CI. et al. Visit-to-visit variation of fasting plasma glucose is a predictor of hip fracture in older persons with type 2 diabetes: the Taiwan Diabetes Study. Osteoporos Int 27, 3587–3597 (2016). https://doi.org/10.1007/s00198-016-3689-1

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