Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer

doi:10.3748/wjg.v31.i3.98688

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World Journal of Gastroenterology

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1007-9327

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Retrospective Cohort Study

World J Gastroenterol. Jan 21, 2025; 31(3): 98688
Published online Jan 21, 2025. doi: 10.3748/wjg.v31.i3.98688

Table 1 Comparison of the clinical and pathological characteristics between the non-diabetes mellitus and diabetes mellitus groups

Variables	Non-DM group (n = 160)	DM group (n = 118)	P value
Age (year, mean ± SD)	57.40 ± 8.31	62.69 ± 8.18	< 0.001^a
Gender (male/female)	99/61	60/58	0.066
BMI > 24 kg/m² (present/absent)	51/109	36/82	0.808
History of smoke (present/absent)	66/94	55/63	0.373
History of drinking (present/absent)	73/87	51/67	0.690
Hypertension (present/absent)	54/106	38/80	0.786
Cardiovascular disease (present/absent)	35/125	24/94	0.757
HbA1c (%, mean ± SD)	5.41 ± 0.33	6.57 ± 1.16	< 0.001^a
FPG (mmol/L, mean ± SD)	4.85 ± 0.56	7.28 ± 2.92	< 0.001^a
CEA (ng/mL, mean ± SD)	44.86 ± 155.54	52.90 ± 176.61	0.688
CA19-9 (ng/mL, mean ± SD)	172.39 ± 1118.65	118.72 ± 921.63	0.671
T stage (3/4)	122/38	82/36	0.208
N stage (1/2)	93/67	76/42	0.289
Tumor location (RCC/LCC)	62/98	49/69	0.640
Tumor size (cm, mean ± SD)	5.12 ± 2.05	4.67 ± 1.92	0.061
Vascular invasion (present/absent)	52/108	31/87	0.262
Perineural invasion (present/absent)	53/107	40/78	0.893
Tumor differentiation (MD/PD)	132/28	95/23	0.672

^aP < 0.05.

DM: Diabetes mellitus; BMI: Body mass index; HbA1c: Glycosylated hemoglobin; FPG: Fasting plasma glucose; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 199; LCC: Left-side colon cancer; RCC: Right-side colon cancer; MD: Moderately differentiated; PD: Poorly differentiated.

Table 2 Comparison of the clinical and pathological characteristics between the well-controlled and poorly controlled groups

Variables	Well-controlled group (n = 73)	Poorly controlled group (n = 45)	P value
Age (year, mean ± SD)	62.55 ± 8.59	62.93 ± 7.55	0.805
Gender (male/female)	35/38	25/20	0.422
BMI > 24 kg/m² (present/absent)	20/53	16/29	0.350
History of smoke (present/absent)	31/42	24/21	0.250
History of drinking (present/absent)	29/44	22/23	0.329
Hypertension (present/absent)	25/48	13/32	0.545
Cardiovascular disease (present/absent)	14/59	10/35	0.690
HbA1c (%, mean ± SD)	5.93 ± 0.56	7.60 ± 1.13	< 0.001^a
FPG (mmol/L, mean ± SD)	6.49 ± 1.91	8.55 ± 3.75	0.001^a
CEA (ng/mL, mean ± SD)	31.27 ± 118.37	87.98 ± 240.80	0.146
CA19-9 (ng/mL, mean ± SD)	28.38 ± 88.07	265.26 ± 1486.75	0.291
T stage (3/4)	51/22	31/14	0.911
N stage (1/2)	48/25	28/17	0.697
Tumor location (RCC/LCC)	29/44	20/25	0.613
Tumor size (cm, mean ± SD)	4.63 ± 1.95	4.73 ± 1.89	0.772
Vascular invasion (present/absent)	21/52	10/35	0.433
Perineural invasion (present/absent)	23/50	17/28	0.485
Tumor differentiation (MD/PD)	56/17	39/6	0.185

^aP < 0.05.

BMI: Body mass index; HbA1c: Glycosylated hemoglobin; FPG: Fasting plasma glucose; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 199; LCC: Left-side colon cancer; RCC: Right-side colon cancer; MD: Moderately differentiated; PD: Poorly differentiated.

Table 3 Comparison of disease-free survival, overall survival and chemoresistance rate in the non-diabetes mellitus, diabetes mellitus, well-controlled and poorly controlled groups, n (%)

	DFS	OS	CRR
Non-DM group (n = 160)	34 (21.25)	27 (16.88)	12 (7.50)
DM group (n = 118)	33 (27.97)	23 (19.50)	17 (14.41)
Well-controlled group (n = 73)	16 (21.90)	10 (13.70)	6 (8.22)
Poorly controlled group (n = 45)	17 (37.78)	13 (28.89)	11 (24.40)
P value¹	0.196	0.575	0.063
P value²	0.908	0.538	0.849
P value³	0.023^a	0.072	0.001^a
P value⁴	0.062	0.043^a	0.015^a

^aP < 0.05.

¹Non-diabetes mellitus group vs diabetes mellitus group.

²Non-diabetes mellitus group vs well-controlled group.

³Non-diabetes mellitus group vs poorly controlled group.

⁴Well-controlled group vs poorly controlled group.

DM: Diabetes mellitus; DFS: Disease-free survival; OS: Overall survival; CRR: Chemoresistance rate.

Table 4 Univariate and multivariate cox regression analysis for disease-free survival and overall survival

Variables	DFS				OS
Variables	HR (95%CI)¹	P value¹	HR (95%CI)²	P value²	HR (95%CI)¹	P value¹	HR (95%CI)²	P value²
Age (≥ 60/< 60), years	1.092 (0.771-1.451)	0.551			1.083 (0.689-1.337)	0.384
Gender (male/female)	1.208 (0.669-1.391	0.804			1.221 (0.773-1.502)	0.448
BMI > 24 kg/m² (present/absent)	1.122 (0.983-1.304)	0.37			1.141 (0.725-1.408)	0.283
History of DM (present/absent)	1.178 (0.694-1.303)	0.327			0.933 (0.791-1.273)	0.739
History of smoke (present/absent)	1.228 (0.993-1.401)	0.225			1.204 (1.033-1.471)	0.131
History of drinking (present/absent)	1.198 (0.989-1.377)	0.336			1.331 (1.085-1.503)	0.106
Hypertension (present/absent)	0.942 (0.793-1.228)	0.601			1.076 (0.880-1.202)	0.441
Cardiovascular disease (present/absent)	1.213 (1.004-1.381)	0.201			1.118 (0.969-1.307)	0.116
CEA (≥ 5/< 5), μg/mL	1.896 (2.231-3.884)	< 0.001	2.031 (1.990-3.551)	0.014	1.974 (1.771-3.025)	< 0.001	1.894 (1.575-2.928)	0.006
CA19-9 (≥ 37/< 37), ng/mL	1.552 (1.383-2.452)	0.017	1.714 (1.508-2.839)	0.021	1.692 (1.493-2.921)	0.032	1.554 (1.399-2.680)	0.041
T stage (4/3)	1.708 (1.620-2.337)	0.015	1.599 (1.483-2.091)	0.044	1.801 (1.674-2.395)	0.009	1.869 (1.503-2.061)	0.029
N stage (2/1)	2.088 (1.854-2.827)	< 0.001	1.880 (1.769-2.557)	0.007	1.822 (1.701-2.223)	0.015	1.777 (1.582-2.330)	0.033
Tumor location (RCC/LCC)	1.695 (1.503-2.241)	0.025	1.597 (1.415-1.998)	0.038	1.839 (1.696-2.377)	0.018	1.683 (1.503-2.117)	0.040
Tumor size (≥ 4.5/< 4.5), cm	2.035 (1.897-2.730)	0.006	1.885 (1.747-2.381)	0.023	1.920 (1.593-2.409)	0.009	1.803 (1.544-2.019)	0.024
Tumor differentiation (PD/MD)	2.913 (1.954-3.409)	< 0.001	2.447 (2.019-2.927)	0.013	1.899 (1.704-2.988)	< 0.001	1.901 (1.695-2.723)	0.018
Vascular invasion (present/absent)	2.189 (1.655-3.231)	< 0.001	2.033 (1.779-2.968)	0.008	1.909 (1.664-2.817)	0.023	1.872 (1.553-2.482)	0.041
Perineural invasion (present/absent)	1.689 (1.347-2.086)	0.030	1.607 (1.306-1.997)	0.039	1.822 (1.606-2.571)	0.008	1.749 (1.500-2.288)	0.036
FPG (≥ 7/< 7), mmol/L	2.829 (2.235-4.026)	< 0.001	2.684 (2.107-3.941)	< 0.001	2.316 (1.994-3.561)	0.002	2.105 (1.890-2.961)	0.019
HbA1c (≥ 7/< 7), %	2.667 (2.403-3.559)	< 0.001	2.344 (2.101-3.285)	0.006	2.258 (2.009-2.891)	0.0012	2.119 (1.943-3.007)	0.021

¹Univariate analysis.

²Multivariate analysis.

DFS: Disease-free survival; OS: Overall survival; HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; DM: Diabetes mellitus; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 199; LCC: Left-side colon cancer; RCC: Right-side colon cancer; MD: Moderately differentiated; PD: Poorly differentiated; FPG: Fasting plasma glucose; HbA1c: Glycosylated hemoglobin.

Table 5 Univariate and multivariate cox regression analysis for chemoresistance rate

Variables	Univariate analysis		Multivariate analysis
Variables	HR (95%CI)	P value	HR (95%CI)	P value
Age (≥ 60/< 60), years	0.872 (0.663-1.025)	0.843
Gender (male/female)	1.004 (0.593-1.118)	0.703
BMI > 24 kg/m² (present/absent)	1.931 (1.658-2.405)	0.007
History of DM (present/absent)	0.997 (0.556-1.200)	0.581
History of smoke (present/absent)	1.074 (0.665-1.209)	0.648
History of drinking(present/absent)	0.837 (0.425-1.102)	0.431
Hypertension (present/absent)	0.915 (0.503-1.220)	0.549
Cardiovascular disease (present/absent)	1.025 (0.694-1.280)	0.331
CEA (≥ 5/< 5), μg/mL	1.231 (0.994-1.398)	0.223
CA19-9 (≥ 37/< 37), ng/mL	1.096 (0.603-1.222)	0.387
T stage (4/3)	1.331 (0.967-1.438)	0.198
N stage (2/1)	1.669 (1.408-2.015)	0.019	1.594 (1.335-1.891)	0.041
Tumor location (RCC/LCC)	1.330 (0.894-1.505)	0.097
Tumor size (≥ 4.5/< 4.5), cm	1.205 (0.983-1.483)	0.105
Tumor differentiation (PD/MD)	1.606 (1.493-1.994)	0.013	1.499 (1.308-1.837)	0.028
Vascular invasion (present/absent)	1.999 (1.784-2.391)	< 0.001	1.803 (1.647-2.089)	0.009
Perineural invasion (present/absent)	1.347 (1.033-1.688)	0.124
FPG (≥ 7/< 7), mmol/L	2.558 (2.147-3.669)	< 0.001	2.214 (1.980-3.014)	0.005
HbA1c (≥ 7/< 7), %	2.867 (2.504-3.771)	< 0.001	2.449 (2.101-3.338)	0.009

HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; DM: Diabetes mellitus; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 199; LCC: Left-side colon cancer; RCC: Right-side colon cancer; MD: Moderately differentiated; PD: Poorly differentiated; FPG: Fasting plasma glucose; HbA1c: Glycosylated hemoglobin.

Citation: Guan RY, Wu JW, Yuan ZY, Liu ZY, Liu ZZ, Xiao ZC, Li JH, Huang CZ, Wang JJ, Yao XQ. Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer. World J Gastroenterol 2025; 31(3): 98688
URL: https://www.wjgnet.com/1007-9327/full/v31/i3/98688.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i3.98688