2型糖尿病患者促甲状腺激素与骨质疏松关系的研究
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摘要
目的研究2型糖尿病患者中骨密度(BMD)与促甲状腺激素水平的关系,探讨2型糖尿病中骨质疏松的可能危险因素。方法收集西安市中心医院内分泌科2017年1月至2018年5月住院的2型糖尿病患者151例,其中男性79例,女性72例。测定一般生化指标、甲状腺功能及骨代谢指标,双能X线骨密度仪测定BMD。对比不同性别之间非骨质疏松(non-OP)及骨质疏松(OP)患者上述指标的差异;Pearson相关分析法分析腰椎及股骨颈BMD与各临床指标之间的关系,多因素logistic回归分析方法探索不同性别组2型糖尿病患者骨质疏松的可能危险因素。结果 1.男性2型糖尿病患者中,non-OP组FT_3较OP组明显升高,女性2型糖尿病患者组OP患者TSH明显高于对照组,BMI明显低于对照组(P<0.05);2.女性腰椎及股骨颈BMD均与TSH负相关(r=-0.290及-0.239 P<0.05),男性BMD与TSH无相关性,无论男女,股骨颈BMD与年龄呈负相关(r=-0.242及-0.363 P<0.05)、与BMI呈正相关(r=0.263及0.469 P<0.05); 3.多因素logistic回归分析示,TSH是女性2型糖尿病患者骨质疏松的主要影响因素(OR=2.581, 95%CI 1.210-5.504,P=0.014。结论 2型糖尿病患者中,随着年龄的增大和BMI的降低骨质疏松发生的风险增高;女性2型糖尿病患者中TSH升高是OP发生的主要危险因素。
Objective To investigate the relationship between osteoporosis and thyrotropin level and the potential risk factors of osteoporosis in patients with type 2 diabetes mellitus(T2DM). Methods 151 patients(79 males and 72 females) with T2 DM in our hospital were selected. BMD of the lumbar spine 1-4(L_(1-4)) and the femoral neck of all the patients were detected using dual-energy X-ray absorptiometry. In different gender group according to the T score, patients were divided into OP group and non-OP group. The differences of general condition and biochemical parameters between the OP group and non-OP group were compared. Pearson correlation analysis was used to analyze the relationship between BMD and clinical indicators. Logistic regression analysis was used to explore the possible risk factors of osteoporosis. Results 1) In male group, FT_3 of non-OP patients was higher than that of OP patients(P<0.05). In the female group there were significant differences in BMI and TSH between OP group and non-OP group(P<0.05). 2) Pearson correlation analysis showed that in female group both lumbar spine and femoral neck BMD were negatively correlated with TSH. Both in men and women, femoral neck BMD was negatively correlated with age(r=-0.242 and-0.363, P<0.05), and positively correlated with BMI(r=0.263 and 0.469, P<0.05). 3) Multivariate logistic regression analysis showed that TSH was the main influencing factor of osteoporosis in female patients with type 2 diabetes(OR=2.581, 95%CI 1.210-5.504, P=0.014). Conclusion In patients with type 2 diabetic, with the increase of age and decrease of BMI, the risk of osteoporosis increases. In elderly females with type 2 diabetic patients, BMD is closely related to the level of TSH. The patients with higher TSH level are more likely to have low BMD.
Objective To investigate the relationship between osteoporosis and thyrotropin level and the potential risk factors of osteoporosis in patients with type 2 diabetes mellitus(T2DM). Methods 151 patients(79 males and 72 females) with T2 DM in our hospital were selected. BMD of the lumbar spine 1-4(L_(1-4)) and the femoral neck of all the patients were detected using dual-energy X-ray absorptiometry. In different gender group according to the T score, patients were divided into OP group and non-OP group. The differences of general condition and biochemical parameters between the OP group and non-OP group were compared. Pearson correlation analysis was used to analyze the relationship between BMD and clinical indicators. Logistic regression analysis was used to explore the possible risk factors of osteoporosis. Results 1) In male group, FT_3 of non-OP patients was higher than that of OP patients(P<0.05). In the female group there were significant differences in BMI and TSH between OP group and non-OP group(P<0.05). 2) Pearson correlation analysis showed that in female group both lumbar spine and femoral neck BMD were negatively correlated with TSH. Both in men and women, femoral neck BMD was negatively correlated with age(r=-0.242 and-0.363, P<0.05), and positively correlated with BMI(r=0.263 and 0.469, P<0.05). 3) Multivariate logistic regression analysis showed that TSH was the main influencing factor of osteoporosis in female patients with type 2 diabetes(OR=2.581, 95%CI 1.210-5.504, P=0.014). Conclusion In patients with type 2 diabetic, with the increase of age and decrease of BMI, the risk of osteoporosis increases. In elderly females with type 2 diabetic patients, BMD is closely related to the level of TSH. The patients with higher TSH level are more likely to have low BMD.
引文
[1] Notarnicola A, Maccagnano G, Tafuri S, et al. Epidemiology of diabetes mellitus in the fragility fracture population of a region of Southern Italy.[J]. Journal of Biological Regulators & Homeostatic Agents, 2016, 30(1):297.
[2] Majumdar S R, Josse R G, Mu L, et al. Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study[J]. Journal of Clinical Endocrinology & Metabolism, 2016, 101(5):1963.
[3] Jung J K, Kim H J, Lee H K, et al. Fracture Incidence and Risk of Osteoporosis in Female Type 2 Diabetic Patients in Korea[J]. Diabetes & Metabolism Journal, 2012, 36(2):144-150.
[4] Rathmann W, Kostev K. Fracture risk in patients with newly diagnosed type 2 diabetes: a retrospective database analysis in primary care[J]. Journal of Diabetes & Its Complications, 2015, 29(6):766-70.
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[8] Abe E; Marians RC; Yu W; Wu XB; Ando T; Li Y; Iqbal J; Eldeiry L; Rajendren G; Blair HC; Davies TF; Zaidi M. TSH Is a Negative Regulator of Skeletal Remodeling[J]. Cell, 2003, 115(2):151-162.
[9] Majumdar S R, Josse R G, Lin M, et al. Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study[J]. Journal of Clinical Endocrinology & Metabolism, 2016, 101(5):1963.
[10] Abe E, Marians RC, Yu W, et al. TSH Is a Negative Regulator of Skeletal Remodeling[J]. Cell, 2003, 115(2):151-162.
[11] Szkudlinski M W, Fremont V, Ronin C, et al. Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships[J]. Physiological Reviews, 2002, 82(2):473-502.
[12] Davies T, Marians R, Latif R. The TSH receptor reveals itself[J]. Journal of Clinical Investigation, 2002, 110(2):161.
[13] G?the S, Wang Z, Ng L, et al. Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation[ J]. Genes Dev, 1999,13 (10): 1329-1341.
[14] Yamoah K, Brebene A, Baliram R, et al. High-mobility group box proteins modulate tumor necrosis factor-alpha expression in osteoclastogenesis via a novel deoxyribonucleic acid sequence.[J]. Molecular Endocrinology, 2008, 22(5):1141-1153.
[15] Bassett J H, O'Shea P J, Sriskantharajah S, et al. Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism.[J]. Molecular Endocrinology, 2007, 21(5):1095.
[16] Lee J S, Fink H A, Vu J, et al. Subclinical Thyroid Dysfunction and Incident Hip Fracture in Older Adults[J]. Archives of Internal Medicine, 2010, 170(21):1876.
[17] 梁利波, 王佑娟, 张玫,等. 亚临床甲状腺功能减退症与骨密度及骨代谢指标的相关性研究[J]. 四川大学学报(医学版), 2014, 45(1):66-69.Liang Libo, Wang Youjuan, Zhang Mei, et al. Study on the correlation between subclinical hypothyroidism and bone mineral density and bone metabolism [J]. Journal of sichuan university (medical edition), 2014, 45(1):66-69. (in Chinese)
[18] Demartini De AC,Kulak AM,Borba VC,et al.Bone mineral density of children and adolescents with congenital hypothyroidism[J].Arq Bras Endocrinol,2007,51(7):1084—1092.
[19] 陈锐雄, 李文锐. 促甲状腺素及其受体与骨质疏松关系的研究进展[J]. 中国骨质疏松杂志, 2007, 13(10):746-749.Chen Ruixiong, Li Wenrui. Research progress in the relationship between thyrotropin and its receptor and osteoporosis [J]. Chinese Journal of osteoporosis, 2007, 13 (10): 746-749.(in chinese)
[20] 郭娟. TSH受体在肥胖鼠甲状腺和脂肪组织中的表达变化[D]. 天津医科大学, 2013.Guo Juan. Expression of TSH receptor in thyroid and adipose tissue of obese rats [D]. Medical University Of Tianjin, 2013.(in Chinese)
[21] Redmond G P. Thyroid dysfunction and women's reproductive health.[J]. Thyroid Official Journal of the American Thyroid Association, 2004, 14 Suppl 1(supplement 1):S5.
[22] 梁君慧, 巩志勇, 赵冰,等. 绝经后妇女骨密度改变与血清激素水平变化[J]. 中国骨质疏松杂志, 2000, 6(1):69-71.Liang Junhui, Gong Zhiyong, Zhao Bing, et al. Changes in bone mineral density and serum hormone levels in postmenopausal women [J]. Chinese Journal of osteoporosis, 2000, 6 (1): 69-71.(in Chinese).
[23] Sayem A S M, Giribabu N, Karim K, et al. Differential expression of the receptors for thyroid hormone, thyroid stimulating hormone, vitamin D and retinoic acid and extracellular signal-regulated kinase in uterus of rats under influence of sex-steroids[J]. Biomedicine & Pharmacotherapy, 2018, 100:132-141.
[24] Szkudlinski M W, Fremont V, Ronin C, et al. Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships[J]. Physiological Reviews, 2002, 82(2):473-502.
[25] Li Y C, Amling M, Pirro A E, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice[J]. Endocrinology, 1998, 139(10):4391-4396.
[26] 刘佳, 徐援, 宁志伟,等. 2型糖尿病患者血清维生素D水平与甲状腺功能的关系研究[J]. 中华内分泌代谢杂志, 2015, 31(3):245-248.Liu Jia, Xu Yuan, Ning Zhiwei, et al. research on the relationship between serum vitamin D level and thyroid function in patients with type 2 diabetes [J]. Journal of endocrine metabolism in China, 2015, 31 (3): 245-248. (in Chinese)
[27] 曹国磊, 王思瑶, 李思源,等. 老年男性2型糖尿病患者骨密度情况及相关影响因素[J]. 中国老年学, 2017, 37(3):612-613.Cao Guolei, Wang Siyao, Li Siyuan, et al. Bone mineral density and related factors in elderly male patients with type 2 diabetes mellitus [J]. Chinese gerontology, 2017, 37 (3): 612-613.(in Chinese).
[28] 薛延. 老年骨质疏松患者骨代谢标志物的检测与应用[J]. 中华老年医学杂志, 2006, 25(6):410-413.Xue Yan. Detection and application of markers of bone metabolism in elderly patients with osteoporosis. [J]. Chinese Journal of Geriatrics, 2006, 25 (6): 410-413.(in Chinese)
[2] Majumdar S R, Josse R G, Mu L, et al. Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study[J]. Journal of Clinical Endocrinology & Metabolism, 2016, 101(5):1963.
[3] Jung J K, Kim H J, Lee H K, et al. Fracture Incidence and Risk of Osteoporosis in Female Type 2 Diabetic Patients in Korea[J]. Diabetes & Metabolism Journal, 2012, 36(2):144-150.
[4] Rathmann W, Kostev K. Fracture risk in patients with newly diagnosed type 2 diabetes: a retrospective database analysis in primary care[J]. Journal of Diabetes & Its Complications, 2015, 29(6):766-70.
[5] Jie W, You W, Jing Z, et al. Increased risk of vertebral fracture in patients with diabetes: a meta-analysis of cohort studies[J]. International Orthopaedics, 2016, 40(6):1299-1307.
[6] Lee W Y, Oh K W, Rhee E J, et al. Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women.[J]. Archives of Medical Research, 2006, 37(4):511-516.
[7] Kim D J, Khang Y H, Koh J M, et al. Low normal TSH levels are associated with low bone mineral density in healthy postmenopausal women[J]. Clinical Endocrinology, 2006, 64(1):86-90.
[8] Abe E; Marians RC; Yu W; Wu XB; Ando T; Li Y; Iqbal J; Eldeiry L; Rajendren G; Blair HC; Davies TF; Zaidi M. TSH Is a Negative Regulator of Skeletal Remodeling[J]. Cell, 2003, 115(2):151-162.
[9] Majumdar S R, Josse R G, Lin M, et al. Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study[J]. Journal of Clinical Endocrinology & Metabolism, 2016, 101(5):1963.
[10] Abe E, Marians RC, Yu W, et al. TSH Is a Negative Regulator of Skeletal Remodeling[J]. Cell, 2003, 115(2):151-162.
[11] Szkudlinski M W, Fremont V, Ronin C, et al. Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships[J]. Physiological Reviews, 2002, 82(2):473-502.
[12] Davies T, Marians R, Latif R. The TSH receptor reveals itself[J]. Journal of Clinical Investigation, 2002, 110(2):161.
[13] G?the S, Wang Z, Ng L, et al. Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation[ J]. Genes Dev, 1999,13 (10): 1329-1341.
[14] Yamoah K, Brebene A, Baliram R, et al. High-mobility group box proteins modulate tumor necrosis factor-alpha expression in osteoclastogenesis via a novel deoxyribonucleic acid sequence.[J]. Molecular Endocrinology, 2008, 22(5):1141-1153.
[15] Bassett J H, O'Shea P J, Sriskantharajah S, et al. Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism.[J]. Molecular Endocrinology, 2007, 21(5):1095.
[16] Lee J S, Fink H A, Vu J, et al. Subclinical Thyroid Dysfunction and Incident Hip Fracture in Older Adults[J]. Archives of Internal Medicine, 2010, 170(21):1876.
[17] 梁利波, 王佑娟, 张玫,等. 亚临床甲状腺功能减退症与骨密度及骨代谢指标的相关性研究[J]. 四川大学学报(医学版), 2014, 45(1):66-69.Liang Libo, Wang Youjuan, Zhang Mei, et al. Study on the correlation between subclinical hypothyroidism and bone mineral density and bone metabolism [J]. Journal of sichuan university (medical edition), 2014, 45(1):66-69. (in Chinese)
[18] Demartini De AC,Kulak AM,Borba VC,et al.Bone mineral density of children and adolescents with congenital hypothyroidism[J].Arq Bras Endocrinol,2007,51(7):1084—1092.
[19] 陈锐雄, 李文锐. 促甲状腺素及其受体与骨质疏松关系的研究进展[J]. 中国骨质疏松杂志, 2007, 13(10):746-749.Chen Ruixiong, Li Wenrui. Research progress in the relationship between thyrotropin and its receptor and osteoporosis [J]. Chinese Journal of osteoporosis, 2007, 13 (10): 746-749.(in chinese)
[20] 郭娟. TSH受体在肥胖鼠甲状腺和脂肪组织中的表达变化[D]. 天津医科大学, 2013.Guo Juan. Expression of TSH receptor in thyroid and adipose tissue of obese rats [D]. Medical University Of Tianjin, 2013.(in Chinese)
[21] Redmond G P. Thyroid dysfunction and women's reproductive health.[J]. Thyroid Official Journal of the American Thyroid Association, 2004, 14 Suppl 1(supplement 1):S5.
[22] 梁君慧, 巩志勇, 赵冰,等. 绝经后妇女骨密度改变与血清激素水平变化[J]. 中国骨质疏松杂志, 2000, 6(1):69-71.Liang Junhui, Gong Zhiyong, Zhao Bing, et al. Changes in bone mineral density and serum hormone levels in postmenopausal women [J]. Chinese Journal of osteoporosis, 2000, 6 (1): 69-71.(in Chinese).
[23] Sayem A S M, Giribabu N, Karim K, et al. Differential expression of the receptors for thyroid hormone, thyroid stimulating hormone, vitamin D and retinoic acid and extracellular signal-regulated kinase in uterus of rats under influence of sex-steroids[J]. Biomedicine & Pharmacotherapy, 2018, 100:132-141.
[24] Szkudlinski M W, Fremont V, Ronin C, et al. Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships[J]. Physiological Reviews, 2002, 82(2):473-502.
[25] Li Y C, Amling M, Pirro A E, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice[J]. Endocrinology, 1998, 139(10):4391-4396.
[26] 刘佳, 徐援, 宁志伟,等. 2型糖尿病患者血清维生素D水平与甲状腺功能的关系研究[J]. 中华内分泌代谢杂志, 2015, 31(3):245-248.Liu Jia, Xu Yuan, Ning Zhiwei, et al. research on the relationship between serum vitamin D level and thyroid function in patients with type 2 diabetes [J]. Journal of endocrine metabolism in China, 2015, 31 (3): 245-248. (in Chinese)
[27] 曹国磊, 王思瑶, 李思源,等. 老年男性2型糖尿病患者骨密度情况及相关影响因素[J]. 中国老年学, 2017, 37(3):612-613.Cao Guolei, Wang Siyao, Li Siyuan, et al. Bone mineral density and related factors in elderly male patients with type 2 diabetes mellitus [J]. Chinese gerontology, 2017, 37 (3): 612-613.(in Chinese).
[28] 薛延. 老年骨质疏松患者骨代谢标志物的检测与应用[J]. 中华老年医学杂志, 2006, 25(6):410-413.Xue Yan. Detection and application of markers of bone metabolism in elderly patients with osteoporosis. [J]. Chinese Journal of Geriatrics, 2006, 25 (6): 410-413.(in Chinese)