Prognostic value of glycated hemoglobin in colorectal cancer

Table 1 Clinical characteristics of colorectal cancer patients - comparison between patients with or without impaired glucose tolerance or type 2 diabetes

	IGT or T2D		P value
	NO (n = 173)	YES (n = 51)
Age (yr)
mean ± SD (range)	64 ± 10 (30-83)	66 ± 8 (54-80)	0.127
Sex, n (%)
Males	103 (60)	30 (59)
Females	70 (40)	21 (41)	0.927
Body mass index
mean ± SD (range)	25.4 ± 4.1 (17.2-38.4)	26.5 ± 4.2 (17.2-38.4)	0.105
HOMA index
Median (IQR)	2.80 (1.83-4.79)	6.48 (3.95-10.26)	< 0.0001
HbA1c
mean ± SD (range)	5.72 ± 0.36 (4.30-7.10)	6.87 ± 1.25 (5.30-13.0)	< 0.0001
Blood lipids (mg/dL)
Total cholesterol	187 ± 42	189 ± 48	0.782
HDL cholesterol	47 ± 12	44 ± 13	0.284
LDL cholesterol	113 ± 38	117 ± 41	0.618
Triglycerides	136 ± 69	138 ± 52	0.838
Site, n (%)
Colon	126 (73)	33 (65)
Rectum	47 (27)	18 (35)	0.293
Histological diagnosis, n (%)
Adenocarcinoma
Mucinous	30 (17)	10 (20)
Non-mucinous	140 (81)	40 (78)
Others1	3 (2)	1 (2)	0.933
ECOG performance status, n (%)
0	150 (91)	40 (82)
1	14 (8)	9 (18)
2	1 (1)	0 (0)	0.129
Stage, n (%)
I	3 (2)	1 (2)
IIA	26 (15)	6 (12)
IIB	4 (2)	1 (2)
IIIA	3 (2)	1 (2)
IIIB	37 (21)	8 (15)
IIIC	9 (5)	5 (10)
Metastatic	91 (53)	29 (57)	0.875

¹Including 3 non diabetic patients with undifferentiated, squamous and mixed neuroendocrine cancers (one each) and one type 2 diabetes (T2D) patient with undifferentiated cancer. CRC: Colorectal cancer; IGT: Impaired glucose tolerance.

Table 2 Glycemic parameters in colorectal cancer patients and non-cancer controls

	CRC	Controls	P value
Overall population	n = 224	n = 112
Fasting blood glucose	106 ± 35	101 ± 39
(mg/dL)	(65-415)	(61-289)	0.219
Fasting insulin (μIU/mL)	14.2 (8.7-23.3)	9.0 (6.0-12.2)	< 0.0001
HbA1c (%)	5.98 ± 0.83	5.63 ± 1.10
	(4.30-13.0)	(3.90-9.70)	0.001
HOMA index	3.5 (2.0-6.1)	2.0 (1.3-3.3)	< 0.0001
Non-diabetic	n = 173	n = 87
Fasting blood glucose	100 ± 25	87 ± 12
(mg/dL)	(65-254)	(61-123)	< 0.0001
Fasting insulin (μIU/mL)	12.5 (8.5-18.6)	7.6 (5.1-10.9)	< 0.0001
HbA1c (%)	5.72 ± 0.36	5.14 ± 0.42
	(4.30-7.10)	(3.90-6.10)	< 0.0001
HOMA index	2.8 (1.8 -4.8)	1.7 (1.0-2.5)	< 0.0001
Non-diabetic normoweight	n = 90	n = 51
Fasting blood glucose	97 ± 19	84 ± 16
(mg/dL)	(65-175)	(61-112)	0.0001
Fasting insulin (μIU/mL)	10.8 (8.1 17.5)	6.5 (4.3-10.0)	< 0.0001
HbA1c (%)	5.69 ± 0.31	5.13 ± 0.40
	(4.70-6.60)	(4.00-6.10)	0.0005
HOMA index	2.5 (1.8-4.0)	1.4 (1.0-2.4)	< 0.0001

Data are reported as mean ± SD (range) or median (interquartile range).

Table 3 Receiver operating characteristics and Bayesian analysis of glycemic parameters

	Fasting blood glucose	Fasting insulin	HOMA-IR	HbA1c
AUC (SE)	0.657 (0.04)	0.728 (0.03)	0.738 (0.03)	0.860 (0.03)
95%CI	0.596-0.714	0.670-0.781	0.680-0.791	0.812-0.900
Criterion	97 mg/dL	12.5 μIU/mL	1.7%	5.4%
Sensitivity	42%	50%	81%	82%
Specificity	85%	84%	55%	82%
+LR (CI)	2.79 (1.63-5.06)	3.09 (1.87-5.41)	1.81 (1.43-2.30)	4.46 (2.96-7.06)
-LR (CI)	0.69 (0.61-0.81)	0.60 (0.52-0.72)	0. 35 (0.24-0.50)	0.22 (0.17-0.30)
P value1	0.0001	0.0001	0.0001	0.0001

¹Two-tailed Fisher Exact test. AUC: Area under the curve; +LR: Positive likelihood ratio; -LR: Negative likelihood ratio.

Table 4 Cox proportional hazards survival regression analysis of the predictive value of clinical-pathological variables and glycemic indexes on progression-free and overall survival of colorectal cancer patients

Variable	Progression-free survival		Overall survival
	HR (95%CI)	P value	HR (95%CI)	P value
Overall population (n = 224)
Sex	0.96 (0.68-1.36)	0.809	0.82 (0.54-1.23)	0.336
Obesity1	0.95 (0.73-1.24)	0.701	0.88 (0.63-1.22)	0.448
Site	0.93 (0.62-1.41)	0.745	0.81 (0.49-1.34)	0.412
Histological diagnosis	0.90 (0.58-1.39)	0.629	0.88 (0.53-1.45)	0.604
Stage of disease2	1.95 (1.11-3.42)	0.021	1.17 (0.58-2.34)	0.662
ECOG-PS	1.54 (0.96-2.47)	0.075	1.84 (1.05-3.23)	0.035
Type of treatment3	1.37 (0.71-2.62)	0.346	1.94 (0.80-4.74)	0.145
Fasting glucose4	0.99 (0.80-1.21)	0.892	1.06 (0.83-1.34)	0.657
Fasting insulin5	0.90 (0.58-1.38)	0.619	1.01 (0.62-1.62)	0.981
Fasting HbA1c6	1.24 (1.01-1.53)	0.040	1.36 (1.05-1.74)	0.018
Non-diabetic patients (n = 173)
Sex	1.05 (0.69-1.59)	0.824	0.79 (0.48-1.31)	0.355
Obesity1	1.11 (0.83-1.50)	0.482	0.91 (0.62-1.34)	0.640
Site	1.09 (0.67-1.76)	0.740	0.98 (0.54-1.79)	0.952
Histological diagnosis	0.91 (0.55-1.52)	0.728	0.88 (0.49-1.61)	0.687
Stage of disease2	1.78 (0.93-3.40)	0.083	0.87 (0.39-1.93)	0.735
ECOG-PS	1.69 (0.98-2.92)	0.060	1.98 (1.02-3.85)	0.044
Type of treatment3	1.46 (0.69-3.08)	0.321	2.93 (1.01-8.56)	0.050
Fasting glucose3	0.94 (0.74-1.20)	0.625	0.91 (0.62-1.22)	0.531
Fasting insulin5	1.01 (0.60-1.68)	0.976	0.91 (0.51-1.64)	0.755
Fasting HbA1c6	1.25 (0.97-1.62)	0.092	1.40 (1.03-1.92)	0.034

¹Coded as normoweight if body mass index (BMI) ≤ 25, overweight if BMI > 25 and ≤ 30, obese if BMI > 30;

²Coded as primary/metastatic;

³Coded as neoadjuvant/adjuvant/metastatic;

⁴Q1: ≤ 87 mg/dL; Q2: > 87 mg/dL and ≤ 97 mg/dL; Q3: > 97 mg/dL and ≤ 117 mg/dL; Q4: > 117 mg/dL;

⁵Q1: ≤ 8.7 μIU/mL; Q2: > 8.7 μIU/mL and ≤ 14 μIU/mL; Q3: > 14 μIU/mL and ≤ 23 μIU/mL; Q4: > 23 μIU/mL;

⁶Q1: ≤ 5.3%; Q2: > 5.3% and ≤ 5.7%; Q3: > 5.7% and ≤ 6.1%; Q4: > 6.1%. ECOG-PS: Eastern Cooperative Oncology Group performance status.