Visceral fat area and red-blood-cell-related indices in adults with type 2 diabetes: Cross-sectional evidence of nonlinear associations

Table 1 Baseline characteristics of the study population according to visceral fat area, n (%)/median (interquartile range)

Characteristic	VFA < 80 cm2 (n = 408)	VFA ≥ 80 cm2 (n = 772)	P value
Age (years)	55.00 (48.00-61.00)	54.00 (44.00-62.00)	0.054
Sex (%)			< 0.001
Female	190 (46.57)	248 (32.12)
Male	218 (53.43)	524 (67.88)
Current drinking			< 0.001
No	295 (75.26)	452 (63.04)
Yes	97 (24.74)	265 (36.96)
Current smoking			< 0.001
No	290 (73.98)	459 (63.84)
Yes	102 (26.02)	260 (36.16)
DBP (mmHg)	74.00 (68.00-78.00)	75.00 (71.00-82.00)	< 0.001
SBP (mmHg)	124.00 (117.00-131.00)	126.00 (120.00-137.00)	< 0.001
HbA1c (%)	9.35 (7.50-11.34)	9.34 (7.55-10.89)	0.224
TC (mmol/L)	4.49 (3.94-5.43)	4.71 (3.95-5.49)	0.164
HDLC (mmol/L)	1.16 (0.99-1.39)	1.05 (0.89-1.24)	< 0.001
LDL-C (mmol/L)	2.73 (2.07-3.44)	2.68 (2.06-3.42)	0.815
TG (mmol/L)	1.54 (1.04-2.64)	2.23 (1.41-3.67)	< 0.001
BMI (kg/m2)	23.00 (21.50-24.40)	26.50 (24.70-28.90)	< 0.001
eGFR (mL/minute/1.73 m2)	103.43 (94.85-112.11)	103.61 (92.88-114.17)	0.649
UA (μmol/L)	287.70 (237.40-345.27)	334.35 (281.93-398.55)	< 0.001
AST (U/L)	16.70 (14.00-21.50)	20.80 (16.10-29.85)	< 0.001
ALT (U/L)	18.80 (13.40-28.90)	27.40 (18.17-46.73)	< 0.001
CRP (mg/L)	1.15 (0.52-2.62)	2.13 (0.93-4.28)	< 0.001
WBC (× 109/L)	5.90 (5.10-7.30)	6.40 (5.40-7.60)	< 0.001
RBC	4.55 (4.23-4.92)	4.75 (4.32-5.14)	< 0.001
HGB	137.00 (126.00-147.00)	142.50 (130.00-153.00)	< 0.001
MCH	30.00 (29.10-30.90)	30.00 (29.10-31.00)	0.575
MCHC	331.00 (325.00-337.00)	332.00 (325.00-340.00)	0.106
PDW	13.40 (11.62-16.08)	13.80 (11.80-16.10)	0.305
MCV	90.40 (87.70-93.00)	90.20 (87.30-93.20)	0.634
HCT	0.42 (0.38-0.44)	0.43 (0.40-0.46)	< 0.001
MPV	11.10 (10.30-12.20)	11.20 (10.30-12.10)	0.626
PLT	187.00 (154.00-223.00)	189.00 (154.00-225.75)	0.892

P values were obtained using the Mann-Whitney U test for continuous variables and the χ² test for categorical variables. VFA: Visceral fat area; DBP: Diastolic blood pressure; SBP: Systolic blood pressure; HbA1c: Glycated hemoglobin; TC: Total cholesterol; TG: Triglycerides; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; BMI: Body mass index; eGFR: Estimated glomerular filtration rate; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; UA: Uric acid; CRP: C-reactive protein; RBC: Red blood cell; WBC: White blood cell; HGB: Hemoglobin; MCV: Mean corpuscular volume; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular hemoglobin concentration; PDW: Platelet distribution width; MPV: Mean platelet volume; HCT: Hematocrit; PLT: Platelet.

Table 2 Association between visceral fat area and hematological indices after multiple imputation (n = 1180)

Exposure	Non-adjusted		Adjust I		Adjust II
	β (95%CI)	P value	β (95%CI)	P value	β (95%CI)	P value
RBC100
VFA	0.27 (0.20-0.35)	< 0.0001	0.15 (0.09-0.22)	< 0.0001	0.20 (0.14-0.26)	< 0.0001
Q1	1.0		1.0		1.0
Q2	9.73 (1.76-17.71)	0.0168	10.60 (4.02-17.18)	0.0016	11.98 (5.74-18.21)	0.0002
Q3	16.33 (8.39-24.28)	< 0.0001	13.44 (6.83-20.05)	< 0.0001	18.69 (12.36-25.03)	< 0.0001
Q4	27.42 (19.45-35.38)	< 0.0001	13.52 (6.85-20.19)	< 0.0001	18.34 (11.91-24.77)	< 0.0001
P for trend	< 0.0001		< 0.0001		< 0.0001
HGB
VFA	0.09 (0.07-0.11)	< 0.0001	0.05 (0.03-0.06)	< 0.0001	0.05 (0.04-0.07)	< 0.0001
Q1	1.0		1.0		1.0
Q2	2.20 (-0.11 to 4.51)	0.0620	2.30 (0.42-4.18)	0.0164	2.41 (0.62-4.19)	0.0082
Q3	4.54 (2.24-6.84)	0.0001	2.94 (1.06-4.83)	0.0022	3.86 (2.05-5.67)	< 0.0001
Q4	8.47 (6.16-10.78)	< 0.0001	3.97 (2.06-5.87)	< 0.0001	4.65 (2.81-6.49)	< 0.0001
P for trend	< 0.0001		< 0.0001		< 0.0001
HCT100
VFA	0.02 (0.02-0.03)	< 0.0001	0.01 (0.01-0.02)	< 0.0001	0.02 (0.01-0.02)	< 0.0001
Q1	1.0		1.0		1.0
Q2	0.75 (0.12-1.39)	0.0205	0.78 (0.24-1.32)	0.0049	0.84 (0.32-1.35)	0.0015
Q3	1.18 (0.55-1.82)	0.0003	0.81 (0.26-1.35)	0.0038	1.17 (0.64-1.69)	< 0.0001
Q4	2.32 (1.69-2.96)	< 0.0001	1.22 (0.67-1.77)	< 0.0001	1.55 (1.02-2.09)	< 0.0001
P for trend	< 0.0001		< 0.0001		< 0.0001
WBC
VFA	0.01 (0.00-0.01)	< 0.0001	0.01 (0.00-0.01)	< 0.0001	0.01 (0.00-0.01)	< 0.0001
Q1	1.0		1.0		1.0
Q2	0.20 (-0.12 to 0.51)	0.2275	0.21 (-0.09 to 0.51)	0.1784	0.22 (-0.08 to 0.53)	0.1478
Q3	0.29 (-0.03 to 0.61)	0.0761	0.33 (0.02-0.64)	0.0349	0.37 (0.06-0.68)	0.0194
Q4	0.85 (0.53-1.17)	< 0.0001	0.69 (0.38-1.01)	< 0.0001	0.72 (0.41-1.04)	< 0.0001
P for trend	< 0.0001		< 0.0001		< 0.0001

Data are regression coefficients (β) and 95% confidence intervals from linear regression models after multiple imputation (n = 1180), examining the associations between visceral fat area and hematological indices. “Non-adjusted” denotes crude models. Model I was adjusted for age and sex. Model II was further adjusted for estimated glomerular filtration rate, current smoking, current drinking, total cholesterol, triglycerides, and glycated hemoglobin. Red blood cell 100 and hematocrit 100 denote the original values multiplied by 100 to facilitate the presentation of regression coefficients. Results for other hematological indices (mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration) are provided in Supplementary Table 1. CI: Confidence interval; VFA: Visceral fat area; RBC: Red blood cell; HGB: Hemoglobin; WBC: White blood cell; HCT: Hematocrit.

Table 3 Threshold effect analysis of the association between visceral fat area and red blood cell indices

	Adjusted β (95%CI)	P value
RBC100
VFA (model I)	0.20 (0.11-0.33)	< 0.0001
VFA (model II)
Inflection point	45 (43-62)
VFA < 45	1.62 (1.15-2.10)	< 0.0001
VFA ≥ 45	0.13 (0.06-0.19)	0.0002
Difference (segment 2-1)	-1.50 (-1.99 to -1.00)	< 0.0001
Log likelihood ratio		< 0.001
HCT100
VFA (model I)	0.02 (0.01-0.03)	< 0.0001
VFA (model II)
Inflection point	45 (43-62)
VFA < 45	0.12 (0.08-0.16)	< 0.0001
VFA ≥ 45	0.01 (0.01-0.02)	0.0415
Difference (segment 2-1)	-0.11 (-0.15 to -0.07)	< 0.0001
Log likelihood ratio		< 0.001
HGB
VFA (model I)	0.05 (0.03-0.09)	< 0.0001
VFA (model II)
Inflection point	45 (43-62)
VFA < 45	0.42 (0.28-0.55)	< 0.0001
VFA ≥ 45	0.03 (0.02-0.05)	0.0004
Difference (segment 2-1)	-0.38 (-0.52 to -0.24)	< 0.0001
Log likelihood ratio		< 0.001
WBC
VFA (model I)	0.01 (0.00-0.01)	< 0.0001
VFA (model II)
Inflection point	66 (50-74.78)
VFA < 66	0.00 (-0.01 to 0.02)	0.5506
VFA ≥ 66	0.01 (0.00-0.01)	< 0.0001
Difference (segment 2-1)	0.00 (-0.01 to 0.02)	0.5512
Log likelihood ratio		0.549

Data are adjusted regression coefficients (β) and 95% confidence intervals from linear (model I) and two-piecewise linear (model II) regression models. Model I assumes a single linear association between visceral fat area (cm²) and each red blood cell index. Model II allows for an inflection point and estimates separate slopes for visceral fat area below and above this point. All models were adjusted for age, sex, estimated glomerular filtration rate, current smoking, current drinking, total cholesterol, triglycerides and glycated hemoglobin. The P value for the log likelihood ratio test compares model II with model I. CI: Confidence interval; VFA: Visceral fat area; RBC: Red blood cell; HGB: Hemoglobin; WBC: White blood cell; HCT: Hematocrit.

Table 4 Subgroup analyses of the associations of hematocrit 100, hemoglobin and red blood cell 100 with visceral fat area

	n	β (95%CI)	P value	P for interaction
HCT100
AGE				0.1218
< 60	784	0.02 (0.01, 0.04)	< 0.0001
≥ 60	396	0.01 (-0.01 to 0.03)	0.1969
Gender				0.0351
Female	438	0.01 (-0.01 to 0.02)	0.5088
Male	742	0.02(-0.01 to 0.03)	< 0.0001
BMI				0.1427
< 28	915	0.03 (0.02, 0.04)	< 0.0001
≥ 28	265	0.001 (-0.02 to 0.02)	0.9269
HbA1c				0.9179
< 7%	141	0.02 (-0.00 to 0.04)	0.1140
≥ 7%	1039	0.02 (0.01, 0.02)	< 0.0001
HGB
AGE				0.3283
< 60	784	0.07 (0.03, 0.11)	0.0003
≥ 60	396	0.04 (-0.01 to 0.10)	0.0976
Gender				0.0412
Female	438	0.01 (-0.04 to 0.06)	0.7775
Male	742	0.07 (0.04, 0.11)	0.0001
BMI				0.0123
< 28	915	0.10 (0.06, 0.14)	< 0.0001
≥ 28	265	-0.02 (-0.09 to 0.06)	0.6664
HbA1c				0.8998
< 7%	141	0.05 (-0.02 to 0.11)	0.1859
≥ 7%	1039	0.05 (0.03, 0.07)	< 0.0001
RBC100
AGE				0.0145
< 60	784	0.34 (0.21, 0.48)	< 0.0001
≥ 60	396	0.06 (-0.13 to 0.25)	0.5542
Gender				0.0202
Female	438	0.02 (-0.16 to 0.20)	0.8251
Male	742	0.30 (0.17, 0.43)	< 0.0001
BMI				0.0013
< 28	915	0.38 (0.23, 0.53)	< 0.0001
≥ 28	265	-0.10 (-0.37 to 0.16)	0.4463
HbA1c				0.7685
< 7%	141	0.16 (-0.07 to 0.38)	0.1659
≥ 7%	1039	0.18 (0.12, 0.25)	< 0.0001

Data are β coefficients with 95% confidence intervals from multivariable linear regression models. Each hematologic index (hematocrit 100, hemoglobin, red blood cell 100, and white blood cell) was the outcome variable, and visceral fat area (cm²) was the exposure. Models were adjusted for covariates as described in the methods (model 3). Missing glycated hemoglobin values were addressed using multiple imputation, allowing all subgroup analyses to include the full cohort (n = 1180). P for interaction was calculated by adding a multiplicative interaction term between visceral fat area and each subgroup variable. Hematocrit and red blood cell were multiplied by 100 for presentation. CI: Confidence interval; AGE: Advanced glycation end products; HCT: Hematocrit; BMI: Body mass index; HbA1c: Glycated hemoglobin; HGB: Hemoglobin; RBC: Red blood cell.