血糖控制与结核病风险: 基于人群队列研究

李晨; 洪忻; 刘巧; 孔雯; 丁晓艳; 竺丽梅; 陆伟; 卢鹏

doi:10.16462/j.cnki.zhjbkz.2022.11.001

血糖控制与结核病风险: 基于人群队列研究

doi: 10.16462/j.cnki.zhjbkz.2022.11.001

李晨¹,
洪忻¹,
刘巧²,
孔雯³,
丁晓艳²,
竺丽梅²,
陆伟^2, ,,
卢鹏^2, ,

1.
210003 南京，南京市疾病预防控制中心慢性传染病防制所
2.
210009 南京，江苏省疾病预防控制中心慢性传染病防制所
3.
201700 上海，上海市青浦区疾病预防控制中心慢性传染病防制所

基金项目:

江苏省卫生健康委科研重点项目 ZD2021052

江苏省卫生健康委科研重点项目 ZDA2020022

详细信息

通讯作者:
陆伟，E-mail: weiluxx@sina.cn

卢鹏，E-mail: lpjscdc@163.com

中图分类号: R181.3
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- 文章访问数: 300
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- 被引次数: 0
出版历程
- 收稿日期: 2022-02-14
- 修回日期: 2022-05-20
- 网络出版日期: 2022-12-21
- 刊出日期: 2022-11-10

Glycemic control and the risk of tuberculosis: a population-based cohort study

LI Chen¹,
HONG Xin¹,
LIU Qiao²,
KONG Wen³,
DING Xiao-yan²,
ZHU Li-mei²,
LU Wei^{2
, ,},
LU Peng^{2
, ,}

1.
Department of Chronic Communicable Disease, Center for Disease Control and Prevention of Nanjing, Nanjing 210003, China
2.
Department of Chronic Communicable Disease, Center for Disease Control and Prevention of Jiangsu Province, Nanjing 210009, China
3.
Department of Chronic Communicable Disease, Center for Disease Control and Prevention of Qingpu District, Shanghai 201700, China

Funds:

Key Scientific Research Project of Jiangsu Commission Health ZD2021052

Key Scientific Research Project of Jiangsu Commission Health ZDA2020022

More Information

Corresponding author: LU Wei, E-mail: weiluxx@sina.cn; LU Peng, E-mail: lpjscdc@163.com

摘要

摘要: 目的探讨血糖控制与结核病发病风险之间的关系。方法在中国东部地区对40 311名研究对象开展队列研究，通过10年的随访，探讨结核病发病的危险因素。排除了基线调查时发现的结核病患者，通过与南京市结核病管理信息系统进行匹配发现结核病患者。主要通过匹配身份证号码、姓名、年龄、出生日期和地址。并建立了Cox比例风险模型，调整了年龄、性别、吸烟状况等因素。结果经过10年(中位随访时间为8.4年)的随访，共发现204名活动性结核病患者，发病密度为59.0/10万人年(95% CI：51.3~67.5)。其中，糖尿病患者有25人，占12.3%，发病密度为71.3/10万人年(95% CI：47.2~103.8)。共发现7名血糖控制不佳糖尿病患者发病，发病密度为84.4/10万人年(95% CI：50.8~132.4)。当把人群按照FPG是否≥7.0 mmol/L分组时，研究发现，与FPG < 7.0 mmol/L相比，FPG≥7.0 mmol/L人群发生结核病的风险提高0.89倍[风险比(hazard ratio, HR)=1.89，95% CI: 1.13~3.13，P=0.014]。结论此次大规模的人群队列研究发现，糖尿病患者血糖控制不佳增加了其发生结核病的风险。因此，加强对血糖控制不佳糖尿病患者的筛查可以及早发现结核病，有利于降低中国结核病的发生与流行。
- 结核分枝杆菌 /
- 糖尿病 /
- 血糖控制 /
- 结核病
Abstract: Objective To evaluate the association between glycemic control among diabetes and active tuberculosis. Methods We conducted a population-based census in eastern China including 40 311 individuals. We investigated risk factors for active tuberculosis by excluding tuberculosis at baseline and linked all participants to the Infectious Disease Reporting Management System and tuberculosis Management Information System of Nanjing City. We followed participants for ten years. We matched participants using unique health identity card numbers, name, age, birthdate, and address. We constructed Cox Proportional hazard models adjusting for age, sex, smoking. Results After 10 years follow-up, 204 individuals progressed to tuberculosis (incidence rate, 71.3 per 100 000 person-years, 95% CI: 51.3-67.5), of whom 25 were diabetes, accounting for 12.3% (incidence rate, 59.0 per 100 000 person-years, 95% CI: 47.2-103.8) and 7 diabetes were with poor glycemic control (incidence rate, 84.4 per 100 000 person-years, 95% CI: 50.8-132.4). Diabetic patients had a significantly higher hazard of tuberculosis [hazard ratio (HR)=1.56, 95% CI: 1.01-2.39, P=0.044]. Diabetics with FPG≥7.0 mmol/L showed nearly one-fold increased risk of active tuberculosis (HR=1.89, 95% CI: 1.13-3.13, P=0.014). Conclusions In this large population-based cohort study in a medium tuberculosis burden region, we found that diabetes increased the hazard of tuberculosis disease and diabetics with poor glycemic control control aggravated this relationship. Strengthening the screening of diabetes patients with poor glycemic control control can improve the efficiency of tuberculosis detection in diabetes patients and help reduce the prevalence of tuberculosis in China.
- Mycobacterium tuberculosis /
- Diabetes /
- Glycemic control /
- Tuberculosis

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图 1 根据血糖控制分层的糖尿病发生结核病的Kaplan-Meier图

Figure 1. Kaplan-Meier curves of tuberculosis in diabetes stratified by glycemic control

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表 1 40 311受试者按照糖尿病分组的人口学特征[n(%)]

Table 1. Demographic characteristics of 40 311 participants stratified by diabetes status [n(%)]

组别	合计	非糖尿病	糖尿病	χ²值	P值
性别				2.34	0.126
女	22 067(54.7)	20 258(54.9)	1 809(53.5)
男	18 244(45.3)	16 671(45.1)	1 573(46.5)
年龄[M(P₂₅, P₇₅), 岁]	50(37，61)	49(35，60)	59(50，67)
BMI(kg/m²)				36.77	< 0.001
< 18.5	1 880(4.7)	1 738(4.7)	142(4.2)
18.5~ < 24.0	22 566(56.3)	20 818(56.7)	1 748(52.1)
24.0~ < 28.0	12 449(31.0)	11 312(30.8)	1 137(33.9)
≥28.0	3 212(8.0)	2 884(7.8)	328(9.8)
吸烟史				4.36	0.035
否	31 566(78.3)	28 966(78.4)	2 600(76.9)
是	8 745(21.7)	7 963(21.6)	782(23.1)
饮酒史				1.02	0.312
否	33 917(84.1)	31 092(84.2)	2 825(83.5)
是	6 394(15.9)	5 837(15.8)	557(16.5)
FPG[M(P₂₅, P₇₅), mmol/L]	5.1(4.6, 5.6)	5.0(4.6, 5.4)	7.2(6.1, 8.5)

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表 2 根据基线糖尿病水平分组的结核病发病密度

Table 2. Tuberculosis incidence rate stratified by diabetes status

分组	发病数(n)	观察人年数(人年)	发病密度(万人年)	发病密度95% CI(万人年)
所有受试者	204	345 793	59.0	51.3~67.5
糖尿病
否	179	383 046	48.6	40.3~54.0
是	25	35 043	71.3	47.2~103.8
血糖控制较好	8	12 677	63.1	29.3~119.8
血糖控制不佳	17	20 134	84.4	50.8~132.4
FPG(mmol/L)
< 7.0	150	326 447	46.0	39.0~53.8
≥7.0	17	20 134	84.4	50.8~132.4

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表 3 结核病发病风险的单因素Cox比例风险模型

Table 3. A univariate Cox proportional risk model for the risk of developing tuberculosis

组别	活动性结核病
组别	发病例数/总人数(% ^a)	HR(95% CI)值	P值
性别
女	82/22 067(0.4)	1.00
男	122/18 244(0.7)	1.80(1.36~2.39)	< 0.001
年龄(岁)		1.00(0.99~1.01)	0.897
BMI(kg/m²)
< 18.5	11/1 880(0.6)	1.00
18.5~ < 24.0	135/22 566(0.6)	1.02(0.55~1.89)	0.943
24.0~ < 28.0	46/12 449(0.4)	0.63(0.33~1.22)	0.170
≥28.0	12/3 212(0.4)	0.64(0.28~1.45)	0.282
吸烟史
否	150/31 566(0.5)	1.00
是	54/8 745(0.6)	1.30(0.95~1.78)	0.096
饮酒史
否	169/33 917(0.5)	1.00
是	35/6 394(0.5)	1.12(0.78~1.61)	0.554
糖尿病
否	179/36 929(0.5)	1.00
是	25/3 382(0.7)	1.53(1.01~2.32)	0.047
血糖控制较好	8/1 219(0.7)	1.35(0.66~2.74)	0.409
血糖控制不佳	17/1 948(0.9)	1.81(1.10~2.98)	0.019
FPG(mmol/L)
< 7.0	150/31 436(0.5)	1.00
≥7.0	17/1 948(0.9)	1.85(1.12~3.05)	0.017
连续性变量		1.08(1.00~1.16)	0.077
注：^a为发病率。

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表 4 结核病发病风险的多因素Cox比例风险模型

Table 4. A multifactorial Cox proportional risk model for the risk of developing tuberculosis

组别	模型Ⅰ		模型Ⅱ		模型Ⅲ		模型Ⅳ
组别	HR(95% CI)值	P值	HR(95% CI)值	P值	HR(95% CI)值	P值	HR(95% CI)值	P值
性别
女	1.00		1.00		1.00		1.00
男	1.89(1.38~2.59)	< 0.001	1.90(1.38~2.60)	< 0.001	1.82(1.27~2.60)	0.001	1.82(1.27~2.60)	0.001
年龄(岁)	1.00(0.99~1.01)	0.609	1.00(0.99~1.01)	0.623	1.00(0.99~1.01)	0.518	1.00(0.99~1.01)	0.592
吸烟史
否	1.00		1.00		1.00		1.00
是	0.90(0.63~1.27)	0.541	0.89(0.63~1.27)	0.524	1.03(0.70~1.51)	0.896	1.03(0.70~1.51)	0.896
糖尿病
否	1.00		1.00
是	1.56(1.01~2.39)	0.044
血糖控制较好			1.37(0.67~2.79)	0.395
血糖控制不佳			1.85(1.12~3.07)	0.017
FPG(mmol/L)
< 7.0					1.00
≥7.0					1.89(1.13~3.13)	0.014
连续性变量							1.07(0.99~1.16)	0.070
注：模型Ⅰ：糖尿病以二分类变量(是、否)纳入模型；模型Ⅱ：糖尿病以三分类变量(否、血糖控制较好、血糖控制不佳)纳入模型；模型Ⅲ：FPG以二分类变量(FPG＜7.0 mmol/L、FPG≥7.0 mmol/L)纳入模型；模型Ⅳ：FPG以连续性变量纳入模型。

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参考文献(27)

[1]	WHO. Global strategy and targets for tuberculosis prevention, care and control after 2015[R]. Geneva: WHO, 2014.
[2]	Raviglione M, Marais B, Floyd K, et al. Scaling up interventions to achieve global tuberculosis control: progress and new developments[J]. Lancet, 2012, 379(9829): 1902-1913. DOI: 10.1016/S0140-6736(12)60727-2.
[3]	Lönnroth K, Roglic G, Harries AD. Improving tuberculosis prevention and care through addressing the global diabetes epidemic: from evidence to policy and practice[J]. Lancet Diabetes Endo, 2014, 2(9): 730-739. DOI: 10.1016/S2213-8587(14)70109-3.
[4]	McMurry HS, Mendenhall E, Rajendrakumar A, et al. Coprevalence of type 2 diabetes mellitus and tuberculosis in low-income and middle-income countries: a systematic review[J]. Diabetes Metab Res Rev, 2019, 35(1): e3066. DOI: 10.1002/dmrr.3066.
[5]	Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies[J]. PLoS Med, 2008, 5(7): e152. DOI: 10.1371/journal.pmed.0050152.
[6]	Stevenson CR, Critchley JA, Forouhi NG, et al. Diabetes and the risk of tuberculosis: a neglected threat to public health?[J]. Chronic Illn, 2007, 3(3): 228-245. DOI: 10.1177/1742395307081502.
[7]	Leegaard A, Riis A, Kornum JB, et al. Diabetes, glycemic control, and risk of tuberculosis: a population-based case-control study[J]. Diabetes Care, 2011, 34(12): 2530-2535. DOI: 10.2337/dc11-0902.
[8]	Lin CH, Kuo SC, Hsieh MC, et al. Effect of diabetes mellitus on risk of latent TB infection in a high TB incidence area: a community-based study in Taiwan[J]. BMJ Open, 2019, 9(10): e029948. DOI: 10.1136/bmjopen-2019-029948.
[9]	Pealing L, Wing K, Mathur R, et al. Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink[J]. BMC Med, 2015, 13: 135. DOI: 10.1186/s12916-015-0381-9.
[10]	Kumpatla S, Sekar A, Achanta S, et al. Characteristics of patients with diabetes screened for tuberculosis in a tertiary care hospital in South India[J]. Public Health Action, 2013, 3(Suppl 1): S23-S28. DOI: 10.5588/pha.13.0035.
[11]	Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies[J]. PLoS Med, 2008, 5(7): e152. DOI: 10.1371/journal.pmed.0050152.
[12]	Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: convergence of two epidemics[J]. Lancet Infect Dis, 2009, 9(12): 737-746. DOI: 10.1016/S1473-3099(09)70282-8.
[13]	Lu P, Zhang Y, Liu Q, et al. Association of BMI, diabetes, and risk of tuberculosis: a population-based prospective cohort[J]. Int J Infect Dis, 2021, 109: 168-173. DOI: 10.1016/j.ijid.2021.06.053.
[14]	Lu P, Liu Q, Zhou Y, et al. Predictors of discordant tuberculin skin test and QuantiFERON-TB Gold In-tube results in Eastern China: a population-based, cohort study[J]. Clin Infect Dis, 2021, 72(11): 2006-2015. DOI: 10.1093/cid/ciaa519.
[15]	Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J]. Diabet Med, 1998, 15(7): 539-553. DOI: 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S.
[16]	Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults[J]. JAMA, 2013, 310(9): 948-959. DOI: 10.1001/jama.2013.168118.
[17]	诸骏仁, 高润霖, 赵水平, 等. 中国成人血脂异常防治指南(2016年修订版)[J]. 中国循环杂志, 2016, 31(10): 937-950. Zhu JR, Gao RL, Zhao SP, et al. Guidelines for the prevention and treatment of dyslipidemia in Chinese adults (revised in 2016)[J]. Chin Cir J, 2016, 31(10): 937-950. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGXH201610002.htm
[18]	Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China[J]. N Engl J Med, 2010, 362(12): 1090-1101. DOI: 10.1056/NEJMoa0908292.
[19]	Bragg F, Holmes MV, Iona A, et al. Association between diabetes and cause-specific mortality in rural and urban areas of China[J]. JAMA, 2017, 317(3): 280-289. DOI: 10.1001/jama.2016.19720.
[20]	Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies[J]. PLoS Med, 2008, 5(7): e152. DOI: 10.1371/journal.pmed.0050152.
[21]	Leung CC, Lam TH, Chan WM, et al. Diabetic control and risk of tuberculosis: a cohort study[J]. Am J Epidemiol, 2008, 167(12): 1486-1494. DOI: 10.1093/aje/kwn075.
[22]	Lee PH, Fu H, Lai TC, et al. Glycemic control and the risk of tuberculosis: a cohort study[J]. PLoS Med, 2016, 13(8): e1002072. DOI: 10.1371/journal.pmed.1002072.
[23]	Baker MA, Lin HH, Chang HY, et al. The risk of tuberculosis disease among persons with diabetes mellitus: a prospective cohort study[J]. Clin Infect Dis, 2012, 54(6): 818-825. DOI: 10.1093/cid/cir939.
[24]	MacRury SM, Gemmell CG, Paterson KR, et al. Changes in phagocytic function with glycaemic control in diabetic patients[J]. J Clin Pathol, 1989, 42(11): 1143-1147. DOI: 10.1136/jcp.42.11.1143.
[25]	Bagdade J, Stewart M, Walters E. Impaired granulocyte adherence: a reversible defect in host defense in patients with poorly controlled diabetes[J]. Diabetes, 1978, 27(6): 677-681. DOI: 10.2337/diab.27.6.677.
[26]	Singhal A, Jie L, Kumar P, et al. Metformin as adjunct antituberculosis therapy[J]. Sci Transl Med, 2014, 6(263): 263ra159. DOI: 10.1126/scitranslmed.3009885.
[27]	Yamashiro S, Kawakami K, Uezu K, et al. Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with Mycobacterium tuberculosis[J]. Clin Exp Immunol, 2005, 139(1): 57-64. DOI: 10.1111/j.1365-2249.2005.02677.x.