住院新诊断2型糖尿病男性患者血浆总睾酮水平与骨钙素的相关性研究

doi:10.16150/j.1671-2870.2021.06.011

摘要/Abstract

摘要：

目的: 探讨住院新诊断男性2型糖尿病患者血浆总睾酮水平与骨钙素水平间的相关性。方法: 收集2018年1月至2020年6月间同济大学附属普陀人民医院收治入院的146例新诊断2型糖尿病男性患者（20~60岁）的临床资料及生化指标,将患者分为性功能正常及减退组,比较2组间的骨钙素水平;并将所有观察对象按骨钙素水平四分位数分为Q1组（<8.0 nmol/L）、Q2组（8.0~10.9 nmol/L）、Q3组（10.9~14.7 nmol/L）、Q4组（≥14.7 nmol/L）,比较组间的糖脂代谢及总睾酮水平差异,采用多元线性回归法分析骨钙素与总睾酮及其他指标间的相关性。结果: 58例（39.72%）男性2型糖尿病患者被诊断为性腺功能减,性腺功能减退组患者的骨钙素水平为（11.27±5.62） nmol/L,性腺功能正常组患者的骨钙素水平为（13.22±5.83） nmol/L,2组间的骨钙素水平差异有统计学意义（P<0.05）。随着骨钙素水平的升高,住院新诊断2型糖尿病男性患者的总睾酮水平升高(P<0.05)。Pearson相关分析显示,患者的骨钙素水平与总睾酮、血肌酐、血钙水平均呈正相关（P<0.05）。偏相关分析显示,在校正年龄、体质量指数（body mass index, BMI）、吸烟、饮酒、血肌酐、血钙、总胆固醇、甘油三酯、空腹胰岛素（fasting insulin, FINS）、糖化血红蛋白（glycosylated hemoglobin, HbA1c）、胰岛素抵抗指数（insulin resistance index, HOMR-IR）后,患者的骨钙素水平仍与总睾酮水平呈显著正相关（P<0.01）。Q4组患者的总睾酮及血钙水平较高,而BMI、HOMR-IR、空腹血糖和HbA1c较低。多元逐步回归分析显示,骨钙素是总睾酮水平的独立影响因素（β值为0.197,P<0.05）。结论: 住院新诊断2型糖尿病男性患者的血浆总睾酮水平与骨钙素水平呈正相关,本研究结果可为糖尿病男性患者性功能障碍的诊治提供参考。

关键词: 新诊断, 总睾酮, 糖尿病,2型, 骨钙素

Abstract:

Objective: To explore the relationship between plasma total testosterone and osteocalcin levels in males with newly diagnosed type 2 diabetes. Methods: A total of 146 males with newly diagnosed type 2 diabetes mellitus admitted from January 2018 through June 2020 were enrolled in the study. The patients were divided into four groups according to the level of osteocalcin: Q1 group (<8.0 nmol/L), Q2 group (8.0-<10.9) nmol/L, Q3 group (10.9-<14.7 nmol/L) and Q4 group (≥14.7 nmol/L). The parameters of glucose and lipid metabolism and total testosterone levels were compared among groups and multiple linear regression was adopted to analyze the relationship of osteocalcin, total testosterone and other indexes. Results: It revealed that 58 (39.72%) patients also had hypogonadism, with the level of osteocalcin decreased to (11.27±5.62) nmol/L, significantly lower than patients with normal gonadal function(13.22±5.83 nmol/L)(P<0.05). The total testosterone level in males with newly diagnosed type 2 diabetes increased along with osteocalcin (P<0.05). Pearson correlation analysis showed that osteocalcin was positively correlated with total testosterone, serum creatinine and serum calcium (P<0.05). Partial correlation analysis showed that after adjusting for age, body mass index (BMI), smoking, drinking, serum creatinine, blood calcium, total cholesterol, triglyceride, fasting insulin (FINS), glycosylated hemoglobin (HbA1c) and insulin resistance index(HOMR-IR), the level of osteocalcin was still positively correlated with total testosterone(P<0.01). Patients with higher osteocalcin had higher levels of total testosterone and blood calcium(Q4 Group), but lower BMI, HOMR-IR, fasting blood glucose and HbA1c. Multiple stepwise regression analysis revealed that high osteocalcin was an independent factor for elevated level of total testosterone (β value 0.197, P<0.05). Conclusions: Plasma total testosterone level is positively correlated with osteocalcin in newly diagnosed male patients with type 2 diabetes mellitus.

Key words: Newly Diagnosed, Total Testosterone, Diabetes, Type 2, Osteocalcin

中图分类号:

R587.1

王广宇, 杨昕, 张立娟, 谭姣容. 住院新诊断2型糖尿病男性患者血浆总睾酮水平与骨钙素的相关性研究[J]. 诊断学理论与实践, 2021, 20(06): 573-578.

WANG Guangyu, YANG Xin, ZHANG Lijuan, TAN Jiaorong. The relationship between plasma total testosterone and osteocalcin levels in males with newly diagnosed type 2 diabetes[J]. Journal of Diagnostics Concepts & Practice, 2021, 20(06): 573-578.

图/表 2

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表2

参考文献 24

[1]	Morton A. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes[J]. J Clin Endocrinol Metab, 2005, 90(3):1903.
[2]	Sepu N, Adeleye JO, Kuti MO. Serum testosterone in Nigerian men with type 2 diabetes mellitus and its relationship with insulin sensitivity and glycemic control[J]. J Natl Med Assoc, 2021, 113(3):285-293.
[3]	Farooq R, Bhat MH, Majid S, et al. Association between T2DM and the lowering of testosterone levels among Kashmiri males[J]. Arch Endocrinol Metab, 2021, 64(5):528-532. doi: 10.20945/2359-3997000000288 pmid: 34033292
[4]	Grossmann M. Testosterone and glucose metabolism in men: current concepts and controversies[J]. J Endocrinol, 2014, 220(3):R37-R55. doi: 10.1530/JOE-13-0393 URL
[5]	Hamahara J, Honda H, Yamamoto K, et al. Clinical characteristics of low androgen status in males with type 2 diabetes mellitus[J]. Acta Med Okayama, 2021, 75(1):1-8. doi: 10.18926/AMO/61424 pmid: 33649607
[6]	Kunutsor SK, Apekey TA, Laukkanen JA. Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence[J]. Eur J Epidemiol, 2015, 30(8):599-614. doi: 10.1007/s10654-015-0058-x pmid: 26085114
[7]	Moser SC, van der Eerden BCJ. Osteocalcin-a versatile bone-derived hormone[J]. Front Endocrinol (Lausanne), 2019, 9:794. doi: 10.3389/fendo.2018.00794 URL
[8]	Turcotte AF, Grenier-Larouche T, Lacombe J, et al. Association between changes in bioactive osteocalcin and glucose homeostasis after biliopancreatic diversion[J]. Endocrine, 2020, 69(3):526-535. doi: 10.1007/s12020-020-02340-2 URL
[9]	Saucedo R, Rico G, Vega G, et al. Osteocalcin, under-carboxylated osteocalcin and osteopontin are not associa-ted with gestational diabetes mellitus but are inversely associated with leptin in non-diabetic women[J]. J Endocrinol Invest, 2015, 38(5):519-526. doi: 10.1007/s40618-014-0220-4 pmid: 25480426
[10]	Jürimäe J, Lätt E, Mäestu J, et al. Osteocalcin is inversely associated with adiposity and leptin in adolescent boys[J]. J Pediatr Endocrinol Metab, 2015, 28(5-6):571-577. doi: 10.1515/jpem-2014-0432 pmid: 25741787
[11]	Deng H, Lu H, Dai Y, et al. Relationship between serum osteocalcin and carotid atherosclerosis in middle-aged men in China: a cross-sectional study[J]. Biomed Res Int, 2018, 2018:1751905.
[12]	田骆冰, 房辉, 徐刚, 等. 中年男性2型糖尿病伴血脂异常患者骨钙素与股动脉内膜中层厚度及下肢动脉斑块的关系[J]. 中华糖尿病杂志, 2020, 12(6):398-403.
[13]	Lee NK, Karsenty G. Reciprocal regulation of bone and energy metabolism[J]. Trends Endocrinol Metab, 2008, 19(5):161-166. doi: 10.1016/j.tem.2008.02.006 URL
[14]	Zhang XL, Wang YN, Ma LY, et al. Uncarboxylated osteocalcin ameliorates hepatic glucose and lipid metabolism in KKAy mice via activating insulin signaling pathway[J]. Acta Pharmacol Sin, 2020, 41(3):383-393. doi: 10.1038/s41401-019-0311-z URL
[15]	Oury F, Sumara G, Sumara O, et al. Endocrine regulation of male fertility by the skeleton[J]. Cell, 2011, 144(5):796-809. doi: 10.1016/j.cell.2011.02.004 URL
[16]	Lombardi G, Perego S, Luzi L, et al. A four-season molecule: osteocalcin. Updates in its physiological roles[J]. Endocrine, 2015, 48(2):394-404. doi: 10.1007/s12020-014-0401-0 URL
[17]	Feldman HA, Longcope C, Derby CA, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study[J]. J Clin Endocrinol Metab, 2002, 87(2):589-598. doi: 10.1210/jcem.87.2.8201 URL
[18]	Lu Y, Li J, Cheng X, et al. Testosterone level in aging male with different glucose tolerance state and its association with osteocalcin[J]. Aging Male, 2019, 22(1):68-73. doi: 10.1080/13685538.2018.1481940 URL
[19]	Abdul Sultan A, Mallen C, Hayward R, et al. Gout and subsequent erectile dysfunction: a population-based cohort study from England[J]. Arthritis Res Ther, 2017, 19(1):123. doi: 10.1186/s13075-017-1322-0 URL
[20]	Lee CH, Olson P, Evans RM. Minireview: lipid metabolism, metabolic diseases, and peroxisome prolifera-tor-activated receptors[J]. Endocrinology, 2003, 144(6):2201-2207. doi: 10.1210/en.2003-0288 URL
[21]	Oury F, Ferron M, Huizhen W, et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis[J]. J Clin Invest, 2013, 123(6):2421-2433. doi: 10.1172/JCI65952 URL
[22]	Dallas SL, Prideaux M, Bonewald LF. The osteocyte: an endocrine cell... and more[J]. Endocr Rev, 2013, 34(5):658-690. doi: 10.1210/er.2012-1026 pmid: 23612223
[23]	Sun L, Kanwar YS. Relevance of TNF-α in the context of other inflammatory cytokines in the progression of diabetic nephropathy[J]. Kidney Int, 2015, 88(4):662-665. doi: 10.1038/ki.2015.250 URL
[24]	Kelly DM, Jones TH. Testosterone and obesity[J]. Obes Rev, 2015, 16(7):581-606. doi: 10.1111/obr.12282 pmid: 25982085

项目	Q1组（n=37）	Q2组（n=37）	Q3组（n=36）	Q4组（n=36）
年龄（岁）	43.89±11.99	42.63±11.25	45.29±11.49	44.50±9.56
BMI(kg/m²)	27.97±4.89	26.68±4.12	26.88±3.76	25.85±4.09^a)
吸烟	14(37.83)	9(24.32)	18(50.00)^b)	14(38.88)
饮酒	2(5.41)	4(10.81)	3(8.33)	5(13.89)
总睾酮(nmol/L)	12.45±6.21	14.59±8.45	15.97±5.63^a)	16.17±5.98^a)
总胆固醇(mmol/L)	5.21(4.51,6.00)	4.74(4.03,5.96)	4.73(4.34,5.30)	4.89(4.07,5.34)
甘油三酯(mmol/L)	1.81(1.39,3.01)	2.34(1.51,3.98)	1.63(1.25,2.40)	1.65(1.24,2.72)
HDL-C(mmol/L)	0.94±0.21	1.02±0.26	0.99±0.22	1.00±0.24
LDL-C(mmol/L)	3.44±0.90	3.15±1.02	3.08±0.65	3.09±0.85
ALT(mmol/L)	37.30(16.00,61.50)	25.80(18.00,45.60)	29.40(17.25,42.55)	23.20(15.25,43.13)
AST(mmol/L)	22.75(15.58,40.00)	24.00(13.60,34.40)	21.10(15.86,29.25)	19.65(14.25,28.86)
血肌酐(μmol/L)	64.74±15.12	73.73±18.50^a)	71.70±10.79	73.73±19.12^c)
尿酸(μmol/L)	340.09±97.82	392.20±110.57^a)	339.43±83.85^b)	338.78±86.92^b)
血钙(mmol/L)	2.22±0.15	2.31±0.13^a)	2.33±0.11^a)	2.34±0.11^a)
血磷(mmol/L)	1.21±0.23	1.17±0.18	1.22±0.23	1.24±0.16
空腹血糖(mmol/L)	12.00(10.01,13.50)	9.35(6.98,13.40)^a)	8.55(6.65,10.65)^a)	8.72(6.95,10.36)^a)
HbA1c（%）	12.40(10.88,13.73)	11.4(9.78,13.00)	10.30(9.05,12.00)^a)	9.50(7.55,10.40)^a),b),c)
FINS(pmol/L)	75.62±40.96	66.48±28.44	60.98±18.07	69.91±47.38
空腹C肽(ng/mL)	1.57±0.82	2.71±1.58	2.21±1.28	1.96±1.17
HOMA-IR	4.86(3.09,7.06)	3.56(1.94,7.32)	3.40(2.07,5.16)^a)	3.17(2.11,5.97)^a)