Abstract

Recent years have witnessed an increased prevalence of knee osteoarthritis (KOA) among diabetes mellitus (DM) patients—conditions which might share common risk factors such as obesity and advanced aging. Therefore, we conducted dry-to-wet lab research approaches to assess the correlation of type 1 DM (T1DM) and type 2 DM (T2DM) with KOA among all age and genders of Taiwanese population. The strength of association (odds ratio: OR) was analyzed using a phenome-wide association study portal. Populations of 37,353 T1DM and 1,218,254 T2DM were included. We observed a significant association of KOA with T1DM (OR: 1.40 (1.33–1.47), p< 0.0001) and T2DM (OR: 2.75 (2.72–2.78), p< 0.0001). The association between T1DM and KOA among the obese (OR: 0.99 (0.54–1.67), p = 0.0477) was insignificant compared to the non-obese (OR: 1.40 (1.33–1.48), p < 0.0001). Interestingly, a higher association between T2DM and KOA among non-obese persons (OR: 2.75, (2.72–2.79), p < 0.0001) compared to the obese (OR: 1.71 (1.55–1.89), p < 0.0001) was noted. Further, histopathologic and Western blot studies of diabetic mice knee joints revealed enhanced carboxymethyl lysine (advanced glycation end product), matrix metalloproteinase-1, and reduced cartilage-specific proteins, including type II collagen (Col II), SOX9, and aggrecan (AGN), indicating deteriorated articular cartilage and proteoglycans. Results indicate that DM is strongly associated with KOA, and obesity may not be a confounding factor.

Original languageEnglish
Article number3021
JournalInternational Journal of Molecular Sciences
Volume19
Issue number10
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

diabetes mellitus
Knee Osteoarthritis
Medical problems
Diabetes Mellitus
obesity
cartilage
Cartilage
Aggrecans
Matrix Metalloproteinase 1
Advanced Glycosylation End Products
Collagen Type II
lysine
Proteoglycans
collagens
Obesity
Collagen
Far-Western Blotting
mice
Aging of materials
Articular Cartilage

Keywords

  • Articular cartilage
  • Diabetes mellitus
  • Knee osteoarthritis
  • Odds ratio
  • Proteoglycan
  • Risk

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Correlation between diabetes mellitus and knee osteoarthritis: A dry-to-wet lab approach. / Dubey, N.K.; Ningrum, D.N.A.; Dubey, R.; Deng, Y.-H.; Li, Yu-Chuan; Wang, Dayen Peter; Wang, J.R.; Syed-Abdul, Shabbir; Deng, Win-Ping.

In: International Journal of Molecular Sciences, Vol. 19, No. 10, 3021, 01.01.2018.

Research output: Contribution to journalArticle

@article{22e0054c7f64425c8e5ac754f420d452,
title = "Correlation between diabetes mellitus and knee osteoarthritis: A dry-to-wet lab approach",
abstract = "Recent years have witnessed an increased prevalence of knee osteoarthritis (KOA) among diabetes mellitus (DM) patients—conditions which might share common risk factors such as obesity and advanced aging. Therefore, we conducted dry-to-wet lab research approaches to assess the correlation of type 1 DM (T1DM) and type 2 DM (T2DM) with KOA among all age and genders of Taiwanese population. The strength of association (odds ratio: OR) was analyzed using a phenome-wide association study portal. Populations of 37,353 T1DM and 1,218,254 T2DM were included. We observed a significant association of KOA with T1DM (OR: 1.40 (1.33–1.47), p< 0.0001) and T2DM (OR: 2.75 (2.72–2.78), p< 0.0001). The association between T1DM and KOA among the obese (OR: 0.99 (0.54–1.67), p = 0.0477) was insignificant compared to the non-obese (OR: 1.40 (1.33–1.48), p < 0.0001). Interestingly, a higher association between T2DM and KOA among non-obese persons (OR: 2.75, (2.72–2.79), p < 0.0001) compared to the obese (OR: 1.71 (1.55–1.89), p < 0.0001) was noted. Further, histopathologic and Western blot studies of diabetic mice knee joints revealed enhanced carboxymethyl lysine (advanced glycation end product), matrix metalloproteinase-1, and reduced cartilage-specific proteins, including type II collagen (Col II), SOX9, and aggrecan (AGN), indicating deteriorated articular cartilage and proteoglycans. Results indicate that DM is strongly associated with KOA, and obesity may not be a confounding factor.",
keywords = "Articular cartilage, Diabetes mellitus, Knee osteoarthritis, Odds ratio, Proteoglycan, Risk",
author = "N.K. Dubey and D.N.A. Ningrum and R. Dubey and Y.-H. Deng and Yu-Chuan Li and Wang, {Dayen Peter} and J.R. Wang and Shabbir Syed-Abdul and Win-Ping Deng",
note = "Export Date: 24 October 2018 通訊地址: Syed-Abdul, S.; Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical UniversityTaiwan; 電子郵件: drshabbir@tmu.edu.tw 參考文獻: Yu, S.H., Chen, S.Y., Li, W.S., Dubey, N.K., Chen, W.H., Chuu, J.J., Leu, S.J., Deng, W.P., Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice (2015) J. Diabetes Res., 2015; Shaw, J.E., Sicree, R.A., Zimmet, P.Z., Global estimates of the prevalence of diabetes for 2010 and 2030 (2010) Diabetes Res. Clin. Pract., 87, pp. 4-14; Shumway, J.T., Gambert, S.R., Diabetic nephropathy-pathophysiology and management (2002) Int. Urol. Nephrol., 34, pp. 257-264; Laakso, M., Pyorala, K., Age of onset and type of diabetes (1985) Diabetes Care, 8, pp. 114-117; Libman, I., Arslanian, S.A., Type II diabetes mellitus: No longer just adults (1999) Pediatr. Ann., 28, pp. 589-593; Rosenbloom, A.L., Joe, J.R., Young, R.S., Winter, W.E., Emerging epidemic of type 2 diabetes in youth (1999) Diabetes Care, 22, pp. 345-354; Brownlee, M., Biochemistry and molecular cell biology of diabetic complications (2001) Nature, 414, pp. 813-820; Vogt, B.W., Schleicher, E.D., Wieland, O.H., Epsilon-Amino-lysine-bound glucose in human tissues obtained at autopsy. Increase in diabetes mellitus (1982) Diabetes, 31, pp. 1123-1127; Steffes, M.W., Affecting the decline of renal function in diabetes mellitus (2001) Kidney Int, 60, pp. 378-379; Fox, C.S., Cardiovascular disease risk factors, type 2 diabetes mellitus, and the Framingham Heart Study (2010) Trends Cardiovasc. Med., 20, pp. 90-95; Smith, A.G., Singleton, J.R., (2012) Diabetic Neuropathy. Continuum (Minneap Minn), 18, pp. 60-84. , PubMed; Onur, T., Wu, R., Metz, L., Dang, A., Characterisation of osteoarthritis in a small animal model of type 2 diabetes mellitus (2014) Bone Joint Res, 3, pp. 203-211; Berenbaum, F., Diabetes-induced osteoarthritis: From a new paradigm to a new phenotype (2011) Ann. Rheum. Dis., 70, pp. 1354-1356; Mayer-Davis, E.J., Lawrence, J.M., Dabelea, D., Divers, J., Isom, S., Dolan, L., Imperatore, G., Pettitt, D.J., Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012 (2017) N. Engl. J. Med., 376, pp. 1419-1429; Olsson, S.E., Degenerative joint disease (Osteoarthrosis): A review with special reference to the dog (1971) J. Small Anim. Pract., 12, pp. 333-342; Stupina, T.A., Shchudlo, N.A., Stepanov, M.A., Structural reorganization of the main joint components during the experimental modeling of osteoarthrosis with reduced blood supply (2014) Morfologiia, 146, pp. 61-65. , PubMed; Benito, M.J., Veale, D.J., Fitzgerald, O., van den Berg, W.B., Bresnihan, B., Synovial tissue inflammation in early and late osteoarthritis (2005) Ann. Rheum. Dis., 64, pp. 1263-1267; Zhuo, Q., Yang, W., Chen, J., Wang, Y., Metabolic syndrome meets osteoarthritis (2012) Nat. Rev. Rheumatol., 8, pp. 729-737; Diagnosis and classification of diabetes mellitus (2009) Diabetes Care, 32, pp. S62-S67; Polsky, S., Ellis, S.L., Obesity, insulin resistance, and type 1 diabetes mellitus (2015) Curr. Opin. Endocrinol. Diabetes Obes., 22, pp. 277-282; Messier, S.P., Obesity and osteoarthritis: Disease genesis and nonpharmacologic weight management (2008) Rheum. Dis. Clin. N. Am., 34, pp. 713-729; Reijman, M., Pols, H.A., Bergink, A.P., Hazes, J.M., Belo, J.N., Lievense, A.M., Bierma-Zeinstra, S.M., Body mass index associated with onset and progression of osteoarthritis of the knee but not of the hip: The Rotterdam Study (2007) Ann. Rheum. Dis., 66, pp. 158-162; Berenbaum, F., Eymard, F., Houard, X., Osteoarthritis, inflammation and obesity (2013) Curr. Opin. Rheumatol., 25, pp. 114-118; Golden, S.H., Brown, A., Cauley, J.A., Chin, M.H., Gary-Webb, T.L., Kim, C., Sosa, J.A., Anton, B., Health disparities in endocrine disorders: Biological, clinical, and nonclinical factors—An Endocrine Society scientific statement (2012) J. Clin. Endocrinol. Metab., 97, pp. E1579-E1639; Syed-Abdul, S., Moldovan, M., Nguyen, P.A., Enikeev, R., Jian, W.S., Iqbal, U., Hsu, M.H., Li, Y.C., Profiling phenome-wide associations: A population-based observational study (2015) J. Am. Med. Inform. Assoc., 22, pp. 896-899. , PubMed; Griffin, T.M., Guilak, F., Why is obesity associated with osteoarthritis? Insights from mouse models of obesity (2008) Biorheology, 45, pp. 387-398; Al-Goblan, A.S., Al-Alfi, M.A., Khan, M.Z., Mechanism linking diabetes mellitus and obesity (2014) Diabetes Metab. Syndr. Obes., 7, pp. 587-591; Buckwalter, J.A., Mankin, H.J., Grodzinsky, A.J., Articular cartilage and osteoarthritis (2005) Instr. Course Lect., 54, pp. 465-480; Glasson, S.S., Chambers, M.G., van Den Berg, W.B., Little, C.B., The OARSI histopathology initiative—Recommendations for histological assessments of osteoarthritis in the mouse (2010) Osteoarthritis Cartilage, 18, pp. S17-S23; Zeng, G.Q., Chen, A.B., Li, W., Song, J.H., Gao, C.Y., High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis (2015) Genet. Mol. Res., 14, pp. 14811-14822; Louati, K., Vidal, C., Berenbaum, F., Sellam, J., Association between diabetes mellitus and osteoarthritis: Systematic literature review and meta-analysis (2015) RMD Open, 1, p. e000077; Saxena, R., Elbers, C.C., Guo, Y., Peter, I., Gaunt, T.R., Mega, J.L., Lanktree, M.B., Li, Y.R., Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci (2012) Am. J. Hum. Genet., 90, pp. 410-425. , PubMed; Zhang, Y., Xu, L., Nevitt, M.C., Aliabadi, P., Yu, W., Qin, M., Lui, L.Y., Felson, D.T., Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: The Beijing Osteoarthritis Study (2001) Arthritis Rheum, 44, pp. 2065-2071; Scavini, M., Stidley, C.A., Shah, V.O., Narva, A.S., Tentori, F., Kessler, D.S., Bobelu, A., Jamon, E., Prevalence of diabetes is higher among female than male Zuni indians (2003) Diabetes Care, 26, pp. 55-60; Hame, S.L., Alexander, R.A., Knee osteoarthritis in women (2013) Curr. Rev. Musculoskelet. Med., 6, pp. 182-187; Hazari, A., Maiya, A.G., Shivashankara, K.N., Agouris, I., Monteiro, A., Jadhav, R., Kumar, S., Mayya, S.S., Kinetics and kinematics of diabetic foot in type 2 diabetes mellitus with and without peripheral neuropathy: A systematic review and meta-analysis (2016) Springerplus, 5, p. 1819; Bijlsma, J.W., Knahr, K., Strategies for the prevention and management of osteoarthritis of the hip and knee (2007) Best Pract. Res. Clin. Rheumatol., 21, pp. 59-76; Li, J., Cesari, M., Liu, F., Dong, B., Vellas, B., Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review (2017) Can. J. Diabetes, 41, pp. 114-119; Twig, G., Afek, A., Derazne, E., Tzur, D., Cukierman-Yaffe, T., Gerstein, H.C., Tirosh, A., Diabetes risk among overweight and obese metabolically healthy young adults (2014) Diabetes Care, 37, pp. 2989-2995; King, L.K., March, L., Anandacoomarasamy, A., Obesity & osteoarthritis (2013) Indian J. Med. Res, 138, pp. 185-193; Peng, B.Y., Chiou, C.S., Dubey, N.K., Yu, S.H., Deng, Y.H., Tsai, F.C., Chiang, H.S., Deng, W.P., Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment (2017) Oncotarget, 8, pp. 97153-97164; Dubey, N.K., Mishra, V.K., Dubey, R., Syed-Abdul, S., Wang, J.R., Wang, P.D., Deng, W.-P., Combating Osteoarthritis through Stem Cell Therapies by Rejuvenating Cartilage: A Review (2018) Stem Cells Int, 2018, p. 13; Vlassara, H., Uribarri, J., Advanced glycation end products (AGE) and diabetes: Cause, effect, or both? (2014) Curr. Diabetes Rep., 14, p. 453; Yoon, H.S., Baik, S.H., Oh, C.H., Quantitative measurement of desquamation and skin elasticity in diabetic patients (2002) Skin Res. Technol., 8, pp. 250-254; Yu, S.H., Dubey, N.K., Li, W.S., Liu, M.C., Chiang, H.S., Leu, S.J., Shieh, Y.H., Deng, W.P., Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice (2016) Plos ONE, 11; Rose, B.J., Kooyman, D.L., A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology (2016) Dis. Mark., 2016; Maldonado, M., Nam, J., The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis (2013) Biomed. Res. Int. 2013; Duquette, J.J., Grigg, P., Hoffman, A.H., The effect of diabetes on the viscoelastic properties of rat knee ligaments (1996) J. Biomech. Eng., 118, pp. 557-564; Lin, H.C., Lee, H.C., Kuo, N.W., Chu, C.H., Hospital characteristics associated with post-discharge suicide of severely depressed patients (2008) J. Affect. Disord., 110, pp. 215-221",
year = "2018",
month = "1",
day = "1",
doi = "10.3390/ijms19103021",
language = "English",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "10",

}

TY - JOUR

T1 - Correlation between diabetes mellitus and knee osteoarthritis: A dry-to-wet lab approach

AU - Dubey, N.K.

AU - Ningrum, D.N.A.

AU - Dubey, R.

AU - Deng, Y.-H.

AU - Li, Yu-Chuan

AU - Wang, Dayen Peter

AU - Wang, J.R.

AU - Syed-Abdul, Shabbir

AU - Deng, Win-Ping

N1 - Export Date: 24 October 2018 通訊地址: Syed-Abdul, S.; Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical UniversityTaiwan; 電子郵件: drshabbir@tmu.edu.tw 參考文獻: Yu, S.H., Chen, S.Y., Li, W.S., Dubey, N.K., Chen, W.H., Chuu, J.J., Leu, S.J., Deng, W.P., Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice (2015) J. Diabetes Res., 2015; Shaw, J.E., Sicree, R.A., Zimmet, P.Z., Global estimates of the prevalence of diabetes for 2010 and 2030 (2010) Diabetes Res. Clin. Pract., 87, pp. 4-14; Shumway, J.T., Gambert, S.R., Diabetic nephropathy-pathophysiology and management (2002) Int. Urol. Nephrol., 34, pp. 257-264; Laakso, M., Pyorala, K., Age of onset and type of diabetes (1985) Diabetes Care, 8, pp. 114-117; Libman, I., Arslanian, S.A., Type II diabetes mellitus: No longer just adults (1999) Pediatr. Ann., 28, pp. 589-593; Rosenbloom, A.L., Joe, J.R., Young, R.S., Winter, W.E., Emerging epidemic of type 2 diabetes in youth (1999) Diabetes Care, 22, pp. 345-354; Brownlee, M., Biochemistry and molecular cell biology of diabetic complications (2001) Nature, 414, pp. 813-820; Vogt, B.W., Schleicher, E.D., Wieland, O.H., Epsilon-Amino-lysine-bound glucose in human tissues obtained at autopsy. Increase in diabetes mellitus (1982) Diabetes, 31, pp. 1123-1127; Steffes, M.W., Affecting the decline of renal function in diabetes mellitus (2001) Kidney Int, 60, pp. 378-379; Fox, C.S., Cardiovascular disease risk factors, type 2 diabetes mellitus, and the Framingham Heart Study (2010) Trends Cardiovasc. Med., 20, pp. 90-95; Smith, A.G., Singleton, J.R., (2012) Diabetic Neuropathy. Continuum (Minneap Minn), 18, pp. 60-84. , PubMed; Onur, T., Wu, R., Metz, L., Dang, A., Characterisation of osteoarthritis in a small animal model of type 2 diabetes mellitus (2014) Bone Joint Res, 3, pp. 203-211; Berenbaum, F., Diabetes-induced osteoarthritis: From a new paradigm to a new phenotype (2011) Ann. Rheum. Dis., 70, pp. 1354-1356; Mayer-Davis, E.J., Lawrence, J.M., Dabelea, D., Divers, J., Isom, S., Dolan, L., Imperatore, G., Pettitt, D.J., Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012 (2017) N. Engl. J. Med., 376, pp. 1419-1429; Olsson, S.E., Degenerative joint disease (Osteoarthrosis): A review with special reference to the dog (1971) J. Small Anim. Pract., 12, pp. 333-342; Stupina, T.A., Shchudlo, N.A., Stepanov, M.A., Structural reorganization of the main joint components during the experimental modeling of osteoarthrosis with reduced blood supply (2014) Morfologiia, 146, pp. 61-65. , PubMed; Benito, M.J., Veale, D.J., Fitzgerald, O., van den Berg, W.B., Bresnihan, B., Synovial tissue inflammation in early and late osteoarthritis (2005) Ann. Rheum. Dis., 64, pp. 1263-1267; Zhuo, Q., Yang, W., Chen, J., Wang, Y., Metabolic syndrome meets osteoarthritis (2012) Nat. Rev. Rheumatol., 8, pp. 729-737; Diagnosis and classification of diabetes mellitus (2009) Diabetes Care, 32, pp. S62-S67; Polsky, S., Ellis, S.L., Obesity, insulin resistance, and type 1 diabetes mellitus (2015) Curr. Opin. Endocrinol. Diabetes Obes., 22, pp. 277-282; Messier, S.P., Obesity and osteoarthritis: Disease genesis and nonpharmacologic weight management (2008) Rheum. Dis. Clin. N. Am., 34, pp. 713-729; Reijman, M., Pols, H.A., Bergink, A.P., Hazes, J.M., Belo, J.N., Lievense, A.M., Bierma-Zeinstra, S.M., Body mass index associated with onset and progression of osteoarthritis of the knee but not of the hip: The Rotterdam Study (2007) Ann. Rheum. Dis., 66, pp. 158-162; Berenbaum, F., Eymard, F., Houard, X., Osteoarthritis, inflammation and obesity (2013) Curr. Opin. Rheumatol., 25, pp. 114-118; Golden, S.H., Brown, A., Cauley, J.A., Chin, M.H., Gary-Webb, T.L., Kim, C., Sosa, J.A., Anton, B., Health disparities in endocrine disorders: Biological, clinical, and nonclinical factors—An Endocrine Society scientific statement (2012) J. Clin. Endocrinol. Metab., 97, pp. E1579-E1639; Syed-Abdul, S., Moldovan, M., Nguyen, P.A., Enikeev, R., Jian, W.S., Iqbal, U., Hsu, M.H., Li, Y.C., Profiling phenome-wide associations: A population-based observational study (2015) J. Am. Med. Inform. Assoc., 22, pp. 896-899. , PubMed; Griffin, T.M., Guilak, F., Why is obesity associated with osteoarthritis? Insights from mouse models of obesity (2008) Biorheology, 45, pp. 387-398; Al-Goblan, A.S., Al-Alfi, M.A., Khan, M.Z., Mechanism linking diabetes mellitus and obesity (2014) Diabetes Metab. Syndr. Obes., 7, pp. 587-591; Buckwalter, J.A., Mankin, H.J., Grodzinsky, A.J., Articular cartilage and osteoarthritis (2005) Instr. Course Lect., 54, pp. 465-480; Glasson, S.S., Chambers, M.G., van Den Berg, W.B., Little, C.B., The OARSI histopathology initiative—Recommendations for histological assessments of osteoarthritis in the mouse (2010) Osteoarthritis Cartilage, 18, pp. S17-S23; Zeng, G.Q., Chen, A.B., Li, W., Song, J.H., Gao, C.Y., High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis (2015) Genet. Mol. Res., 14, pp. 14811-14822; Louati, K., Vidal, C., Berenbaum, F., Sellam, J., Association between diabetes mellitus and osteoarthritis: Systematic literature review and meta-analysis (2015) RMD Open, 1, p. e000077; Saxena, R., Elbers, C.C., Guo, Y., Peter, I., Gaunt, T.R., Mega, J.L., Lanktree, M.B., Li, Y.R., Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci (2012) Am. J. Hum. Genet., 90, pp. 410-425. , PubMed; Zhang, Y., Xu, L., Nevitt, M.C., Aliabadi, P., Yu, W., Qin, M., Lui, L.Y., Felson, D.T., Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: The Beijing Osteoarthritis Study (2001) Arthritis Rheum, 44, pp. 2065-2071; Scavini, M., Stidley, C.A., Shah, V.O., Narva, A.S., Tentori, F., Kessler, D.S., Bobelu, A., Jamon, E., Prevalence of diabetes is higher among female than male Zuni indians (2003) Diabetes Care, 26, pp. 55-60; Hame, S.L., Alexander, R.A., Knee osteoarthritis in women (2013) Curr. Rev. Musculoskelet. Med., 6, pp. 182-187; Hazari, A., Maiya, A.G., Shivashankara, K.N., Agouris, I., Monteiro, A., Jadhav, R., Kumar, S., Mayya, S.S., Kinetics and kinematics of diabetic foot in type 2 diabetes mellitus with and without peripheral neuropathy: A systematic review and meta-analysis (2016) Springerplus, 5, p. 1819; Bijlsma, J.W., Knahr, K., Strategies for the prevention and management of osteoarthritis of the hip and knee (2007) Best Pract. Res. Clin. Rheumatol., 21, pp. 59-76; Li, J., Cesari, M., Liu, F., Dong, B., Vellas, B., Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review (2017) Can. J. Diabetes, 41, pp. 114-119; Twig, G., Afek, A., Derazne, E., Tzur, D., Cukierman-Yaffe, T., Gerstein, H.C., Tirosh, A., Diabetes risk among overweight and obese metabolically healthy young adults (2014) Diabetes Care, 37, pp. 2989-2995; King, L.K., March, L., Anandacoomarasamy, A., Obesity & osteoarthritis (2013) Indian J. Med. Res, 138, pp. 185-193; Peng, B.Y., Chiou, C.S., Dubey, N.K., Yu, S.H., Deng, Y.H., Tsai, F.C., Chiang, H.S., Deng, W.P., Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment (2017) Oncotarget, 8, pp. 97153-97164; Dubey, N.K., Mishra, V.K., Dubey, R., Syed-Abdul, S., Wang, J.R., Wang, P.D., Deng, W.-P., Combating Osteoarthritis through Stem Cell Therapies by Rejuvenating Cartilage: A Review (2018) Stem Cells Int, 2018, p. 13; Vlassara, H., Uribarri, J., Advanced glycation end products (AGE) and diabetes: Cause, effect, or both? (2014) Curr. Diabetes Rep., 14, p. 453; Yoon, H.S., Baik, S.H., Oh, C.H., Quantitative measurement of desquamation and skin elasticity in diabetic patients (2002) Skin Res. Technol., 8, pp. 250-254; Yu, S.H., Dubey, N.K., Li, W.S., Liu, M.C., Chiang, H.S., Leu, S.J., Shieh, Y.H., Deng, W.P., Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice (2016) Plos ONE, 11; Rose, B.J., Kooyman, D.L., A Tale of Two Joints: The Role of Matrix Metalloproteases in Cartilage Biology (2016) Dis. Mark., 2016; Maldonado, M., Nam, J., The role of changes in extracellular matrix of cartilage in the presence of inflammation on the pathology of osteoarthritis (2013) Biomed. Res. Int. 2013; Duquette, J.J., Grigg, P., Hoffman, A.H., The effect of diabetes on the viscoelastic properties of rat knee ligaments (1996) J. Biomech. Eng., 118, pp. 557-564; Lin, H.C., Lee, H.C., Kuo, N.W., Chu, C.H., Hospital characteristics associated with post-discharge suicide of severely depressed patients (2008) J. Affect. Disord., 110, pp. 215-221

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Recent years have witnessed an increased prevalence of knee osteoarthritis (KOA) among diabetes mellitus (DM) patients—conditions which might share common risk factors such as obesity and advanced aging. Therefore, we conducted dry-to-wet lab research approaches to assess the correlation of type 1 DM (T1DM) and type 2 DM (T2DM) with KOA among all age and genders of Taiwanese population. The strength of association (odds ratio: OR) was analyzed using a phenome-wide association study portal. Populations of 37,353 T1DM and 1,218,254 T2DM were included. We observed a significant association of KOA with T1DM (OR: 1.40 (1.33–1.47), p< 0.0001) and T2DM (OR: 2.75 (2.72–2.78), p< 0.0001). The association between T1DM and KOA among the obese (OR: 0.99 (0.54–1.67), p = 0.0477) was insignificant compared to the non-obese (OR: 1.40 (1.33–1.48), p < 0.0001). Interestingly, a higher association between T2DM and KOA among non-obese persons (OR: 2.75, (2.72–2.79), p < 0.0001) compared to the obese (OR: 1.71 (1.55–1.89), p < 0.0001) was noted. Further, histopathologic and Western blot studies of diabetic mice knee joints revealed enhanced carboxymethyl lysine (advanced glycation end product), matrix metalloproteinase-1, and reduced cartilage-specific proteins, including type II collagen (Col II), SOX9, and aggrecan (AGN), indicating deteriorated articular cartilage and proteoglycans. Results indicate that DM is strongly associated with KOA, and obesity may not be a confounding factor.

AB - Recent years have witnessed an increased prevalence of knee osteoarthritis (KOA) among diabetes mellitus (DM) patients—conditions which might share common risk factors such as obesity and advanced aging. Therefore, we conducted dry-to-wet lab research approaches to assess the correlation of type 1 DM (T1DM) and type 2 DM (T2DM) with KOA among all age and genders of Taiwanese population. The strength of association (odds ratio: OR) was analyzed using a phenome-wide association study portal. Populations of 37,353 T1DM and 1,218,254 T2DM were included. We observed a significant association of KOA with T1DM (OR: 1.40 (1.33–1.47), p< 0.0001) and T2DM (OR: 2.75 (2.72–2.78), p< 0.0001). The association between T1DM and KOA among the obese (OR: 0.99 (0.54–1.67), p = 0.0477) was insignificant compared to the non-obese (OR: 1.40 (1.33–1.48), p < 0.0001). Interestingly, a higher association between T2DM and KOA among non-obese persons (OR: 2.75, (2.72–2.79), p < 0.0001) compared to the obese (OR: 1.71 (1.55–1.89), p < 0.0001) was noted. Further, histopathologic and Western blot studies of diabetic mice knee joints revealed enhanced carboxymethyl lysine (advanced glycation end product), matrix metalloproteinase-1, and reduced cartilage-specific proteins, including type II collagen (Col II), SOX9, and aggrecan (AGN), indicating deteriorated articular cartilage and proteoglycans. Results indicate that DM is strongly associated with KOA, and obesity may not be a confounding factor.

KW - Articular cartilage

KW - Diabetes mellitus

KW - Knee osteoarthritis

KW - Odds ratio

KW - Proteoglycan

KW - Risk

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U2 - 10.3390/ijms19103021

DO - 10.3390/ijms19103021

M3 - Article

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 10

M1 - 3021

ER -