Clinical characteristics and risk factor analysis of type 2 diabetes mellitus complicated with cryptococcal meningitis

doi:10.3969/j.issn.1004-583X.2025.05.007

Abstract

Abstract:

Objective To analyze the clinical characteristics of type 2 diabetes mellitus (T2DM) complicated with cryptococcal meningitis, and to identify potential risk factors associated with an unfavorable prognosis. Methods Clinical data of 49 T2DM patients complicated with cryptococcal meningitis who were admitted from January 2021 to May 2023 were retrospectively analyzed. Forty-nine T2DM outpatients were randomly selected as the control group. The collected data encompassed basic information, medical history, laboratory test results, and prognosis. Results T2DM patients complicated with cryptococcal meningitis showed significantly elevated levels of white blood cell and neutrophil counts compared to the control group, while hemoglobin and albumin levels were significantly lower (P<0.05).Moreover, there was a significantly higher proportion of intracranial pressure >300 cmH₂O(1 cmH₂O=0.098 kPa) in T2DM patients complicated with cryptococcal meningitis who have complications than T2DM patients complicated with cryptococcal meningitis who have not complications (P=0.033). Significantly lower levels of neutrophil count and fasting blood glucose were seen in the good prognosis group compared to the poor prognosis group (P=0.046, and P=0.005, respectively). A significantly lower incidence of T2DM-associated complications was also detected in the good prognosis group than the poor prognosis group (P=0.047). Conclusion T2DM patients with lower levels of hemoglobin and albumin suffer from an increased susceptibility to cryptococcal meningitis. Furthermore, increased inflammation level, inadequate blood glucose control, and the presence of complications are associated with an elevated risk of poor prognosis in them.

Key words: diabetes mellitus, type 2, cryptococcus, cryptococcal meningitis, clinical characteristics, risk factors

CLC Number:

R587.1

Xiao Ke, Wang Qi. Clinical characteristics and risk factor analysis of type 2 diabetes mellitus complicated with cryptococcal meningitis[J]. Clinical Focus, 2025, 40(5): 423-427.

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URL: http://www.lchc.cn/EN/10.3969/j.issn.1004-583X.2025.05.007

http://www.lchc.cn/EN/Y2025/V40/I5/423

Figures/Tables 4

References 19

[1]	Li Y, Fang W, Jiang W, et al. Cryptococcosis in patients with diabetes mellitus II in mainland China: 1993-2015[J]. Mycoses, 2017, 60(11):706-713. doi: 10.1111/myc.12645 pmid: 28857298
[2]	Gregg EW, Cheng YJ, Srinivasan M, et al. Trends in cause-specific mortality among adults with and without diagnosed diabetes in the USA: An epidemiological analysis of linked national survey and vital statistics data[J]. Lancet, 2018, 391(10138):2430-2440. doi: S0140-6736(18)30314-3 pmid: 29784146
[3]	Lao M, Li C, Li J, et al. Opportunistic invasive fungal disease in patients with type 2 diabetes mellitus from Southern China: Clinical features and associated factors[J]. J Diabetes Investig, 2020, 11(3):731-744.
[4]	Nguyen MH, Husain S, Clancy CJ, et al. Outcomes of central nervous system cryptococcosis vary with host immune function: Results from a multi-center, prospective study[J]. J Infect, 2010, 61(5):419-426. doi: 10.1016/j.jinf.2010.08.004 pmid: 20732350
[5]	Gassiep I, Aye C, Armstrong M, et al. Correlation between serum cryptococcal antigen titre and meningitis in immunocompetent patients[J]. J MedMicrobiol, 2018, 67(10):1515-1518.
[6]	Temfack E, Boyer-Chammard T, Lawrence D, et al. New insights into Cryptococcus spp. biology and cryptococcal meningitis[J]. Curr Neurol Neurosci Rep, 2019, 19(10):10-81.
[7]	Shirley RM, Baddley JW. Cryptococcal lung disease[J]. Curr OpinPulm Med, 2009, 15(3):254-260.
[8]	Yamamoto Y, Kohno S, Koga H, et al. Random amplified polymorphic DNA analysis of clinically and environmentally isolated Cryptococcus neoformans in Nagasaki[J]. J Clin Microbiol, 1995, 33(12):3328-3332. doi: 10.1128/jcm.33.12.3328-3332.1995 pmid: 8586730
[9]	Sorrell TC, Chen SCA, Ruma P, et al. Concordance of clinical and environmental isolates of Cryptococcus neoformans var. gattii by random amplification of polymorphic DNA analysis and PCR fingerprinting[J]. J Clin Microbiol, 1996, 34(5):1253-1260. doi: 10.1128/jcm.34.5.1253-1260.1996 pmid: 8727912
[10]	Rolfes MA, Hullsiek KH, Rhein J, et al. The effect of therapeutic lumbar punctures on acute mortality from cryptococcal meningitis[J]. Clin Infect Dis, 2014, 59(11):1607-1614. doi: 10.1093/cid/ciu596 pmid: 25057102
[11]	Van der Horst CM, Saag MS, Cloud GA, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome[J]. N Engl J Med, 1997, 337(1):15-21.
[12]	Tsai ST, Lin FY, Chen PS, et al. Three-year mortality in cryptococcal meningitis: Hyperglycemia predict unfavorable outcome[J]. PLoS One, 2021, 16(5):e0251749.
[13]	Tessaro FHG, Ayala TS, Nolasco EL, et al. Insulin Influences LPS-Induced TNF-α and IL-6 release through distinct pathways in mouse macrophages from different compartments[J]. Cell Physiol Biochem, 2017, 42(5):2093-2104. doi: 10.1159/000479904 pmid: 28810254
[14]	Kumar M, Roe K, Nerurkar PV, et al. Reduced immune cell infiltration and increased pro-inflammatory mediators in the brain of type 2 diabetic mouse model infected with West Nile virus[J]. J Neuroinflammation, 2014, 21, 11:80.
[15]	Martinez N, Ketheesan N, Martens GW, et al. Defects in early cell recruitment contribute to the increased susceptibility to respiratory Klebsiella pneumoniae infection in diabetic mice[J]. Microbes Infect, 2016, 18(10):649-655. doi: S1286-4579(16)30068-5 pmid: 27256462
[16]	Perner A, Nielsen SE, Rask-Madsen J. High glucose impairs superoxide production from isolated blood neutrophils[J]. Intensive Care Med, 2003, 29(4):642-645.
[17]	Tao Z, Pu Q, Shen Y, et al. Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis[J]. BMC Infect Dis, 2024, 24(1):1018. doi: 10.1186/s12879-024-09895-9 pmid: 39304813
[18]	Favretto G, Cunha RSD, Dalboni MA, et al. Endothelial microparticles in uremia: Biomarkers and potential therapeutic targets[J]. Toxins (Basel), 2019, 11(5):267.
[19]	Rocha MF, Bain HDC, Stone N, et al. Reframing the clinical phenotype and management of cryptococcal meningitis[J]. Pract Neurol, 2025, 25(1):25-39.

临床特征	脑膜炎组(n=49)	对照组(n=49)	统计值	P值
男性[例(%)]	33(67.3)	35(71.4)	χ²=0.194	0.661
年龄(岁)	55±11	57±13	t=0.597	0.551
白细胞(×10⁹/L)	7.96±3.47	6.67±1.80	t=2.314	0.024
中性粒细胞(×10⁹/L)	5.92±3.17	4.02±1.45	t=4.024	0.000
血红蛋白(g/L)	121±24	139±17	t=4.533	0.000
血小板(×10⁹/L)	225±82	230±53	t=0.318	0.752
尿素(mmol/L)	6.58±2.86	6.51±2.20	t=0.118	0.906
白蛋白(g/L)	37.8±5.5	43.4±6.8	t=4.682	0.000
肌酐(μmol/L)	78±40	78±26	t=0.021	0.983
空腹血糖(mmol/L)	8.79±4.15	9.24±5.86	t=0.441	0.660
糖化血红蛋白(%)	6.7±1.5	7.3±2.2	t=1.331	0.186
降钙素原(μg/L)	0.13±0.18	-	-	-

临床特征	脑膜炎组(n=49)	对照组(n=49)	统计值	P值
男性[例(%)]	33(67.3)	35(71.4)	χ²=0.194	0.661
年龄(岁)	55±11	57±13	t=0.597	0.551
白细胞(×10⁹/L)	7.96±3.47	6.67±1.80	t=2.314	0.024
中性粒细胞(×10⁹/L)	5.92±3.17	4.02±1.45	t=4.024	0.000
血红蛋白(g/L)	121±24	139±17	t=4.533	0.000
血小板(×10⁹/L)	225±82	230±53	t=0.318	0.752
尿素(mmol/L)	6.58±2.86	6.51±2.20	t=0.118	0.906
白蛋白(g/L)	37.8±5.5	43.4±6.8	t=4.682	0.000
肌酐(μmol/L)	78±40	78±26	t=0.021	0.983
空腹血糖(mmol/L)	8.79±4.15	9.24±5.86	t=0.441	0.660
糖化血红蛋白(%)	6.7±1.5	7.3±2.2	t=1.331	0.186
降钙素原(μg/L)	0.13±0.18	-	-	-

临床特征	例数	阳性率(%)	中位数
脑脊液CrAg检测	49	49(100.00)	-
墨汁染色检测	49	18(36.73)	0(0, 22)
脑脊液白细胞>10×10⁶/L	49	37(75.51)	46(95, 182)
脑脊液蛋白>450 mg/L	49	34(69.39)	0.74(0.41, 1.28)
脑脊液氯化物<120 mmol/L	49	14(28.57)	122.40(118.45, 126.25)
脑脊液糖<2.5 mmol/L	49	16(32.65)	3.06(2.07, 4.21)
颅内压>300 cmH₂O	38	14(36.84)	210(130, 330)

临床特征	例数	阳性率(%)	中位数
脑脊液CrAg检测	49	49(100.00)	-
墨汁染色检测	49	18(36.73)	0(0, 22)
脑脊液白细胞>10×10⁶/L	49	37(75.51)	46(95, 182)
脑脊液蛋白>450 mg/L	49	34(69.39)	0.74(0.41, 1.28)
脑脊液氯化物<120 mmol/L	49	14(28.57)	122.40(118.45, 126.25)
脑脊液糖<2.5 mmol/L	49	16(32.65)	3.06(2.07, 4.21)
颅内压>300 cmH₂O	38	14(36.84)	210(130, 330)

临床特征	合并并发症(n=8)	未合并并发症(n=41)	统计值	P值
住院时间>20 d[例(%)]	0	11(26.8)	-	0.172
白细胞(×10⁹/L)	8.42±3.54	7.87±3.50	t=0.403	0.689
中性粒细胞(×10⁹/L)	5.97±3.59	5.92±3.13	t=0.044	0.965
血红蛋白(g/L)	133±19	118±25	t=1.581	0.121
血小板(×10⁹/L)	208±82	229±83	t=0.660	0.512
尿素(mmol/L)	7.44±4.96	6.41±2.31	t=0.931	0.357
白蛋白(g/L)	36.2±4.5	38.2±5.7	t=0.915	0.365
肌酐(μmol/L)	108±74	72±28	t=1.370	0.211
空腹血糖(mmol/L)	7.91±3.55	8.96±4.27	t=0.653	0.517
糖化血红蛋白(%)	7.0±1.4	6.7±1.5	t=0.395	0.695
降钙素原(μg/L)	0.13±0.18	0.13±0.19	t=0.037	0.971
墨汁染色计数>1 000/ml[例(%)]	1(12.5)	9(22.0)	-	1.000
脑脊液白细胞(×10⁶/L)	110±123	141±213	t=0.399	0.692
脑脊液蛋白(mg/L)	0.956±0.422	1.214±1.461	t=0.490	0.626
脑脊液氯化物(mmol/L)	121.7±5.0	121.7±7.6	t=0.001	0.999
脑脊液糖(mmol/L)	2.85±1.42	3.12±1.24	t=0.556	0.581
颅内压>300 cmH₂O[例(%)]	5(62.5)	9(22.0)	χ²=5.293	0.033
V-P分流术史[例(%)]	4(50.0)	21(51.2)	-	1.000
合并细菌感染[例(%)]	1(12.5)	4(9.8)	-	1.000
吸烟史[例(%)]	0	5(12.2)	-	0.575
饮酒史[例(%)]	0	2(4.9)	-	1.000
高血压[例(%)]	2(25.0)	18(43.9)	-	0.445
贫血[例(%)]	2(25.0)	19(46.3)	-	0.438
低蛋白血症[例(%)]	2(25.0)	13(31.7)	χ²=0.000	1.000
高脂血症[例(%)]	5(62.5)	22(53.6)	-	0.715