Associations Between Serum Folate Level and HOMA-IR in Chinese Patients with Type 2 Diabetes Mellitus

Figures & data

Table 1 Comparison of Baseline Data Between T2DM Group and NC Group

Variables		Total (n=412)	T2DM (n=206)	NC (n=206)	P-value
General physical indicators	Gender, male, n (%)	202 (49.02)	83 (40.29)	119 (57.77)	<0.001
	Age, years	50.60 (±12.10)	50.96 (±13.98)	50.24 (±9.84)	0.548
	Height, cm	167.00 (161.00, 173.00)	168.00 (161.00, 173.00)	166.00 (161.00, 173.00)	0.355
	Weight, kg	70.00 (62.00, 80.00)	74.60 (64.60, 84.00)	68.00 (59.00, 75.00)	<0.001
	BMI, kg/m^2	25.71 (±4.10)	26.95 (±4.43)	24.45 (±3.29)	<0.001
	WC, cm	89.00 (81.00, 97.00)	92.00 (85.00, 100.00)	85.00 (78.00, 91.00)	<0.001
	SBP, mmHg	127.00 (114.00, 140.00)	131.00 (120.00, 145.00)	121.00 (110.00, 137.00)	<0.001
	DBP, mmHg	82.12 (±11.98)	83.29 (±12.38)	80.94 (±11.45)	0.047
	Diabetes duration, years	6.41 (±7.02)	6.41 (±7.02)	-	-
	Smoking history, n (%)	83 (20.15)	45 (21.85)	38 (18.45)	0.390
	Alcohol history, n (%)	116 (28.16)	38 (18.45)	78 (37.86)	<0.001
Blood lipid indices	TC, mmol/L	4.98 (4.28, 5.57)	4.89 (4.02, 5.69)	5.02 (4.46, 5.48)	0.305
	TG, mmol/L	1.30 (0.93, 2.08)	1.65 (1.10, 2.63)	1.08 (0.86, 1.50)	<0.001
	HDL-C, mmol/L	1.23 (1.01, 1.49)	1.04 (0.91, 1.23)	1.42 (1.23, 1.65)	<0.001
	LDL-C, mmol/L	3.18 (2.66, 3.69)	3.19 (2.62, 3.81)	3.12 (2.70, 3.59)	0.418
	ApoB, g/L	0.90 (0.73, 1.06)	0.94 (0.77, 1.12)	0.86 (0.70, 1.02)	<0.001
Hepatic function indices	AST, U/L	20.10 (17.10, 24.60)	20.20 (16.50, 29.00)	19.90 (17.70, 23.10)	0.218
	ALT, U/L	18.60 (14.00, 27.10)	21.40 (15.00, 32.20)	17.10 (12.90, 22.50)	<0.001
	GGT, U/L	22.10 (15.90, 34.20)	25.70 (18.60, 40.80)	19.00 (14.10, 28.80)	<0.001
	TBIL, µmol/L	14.10 (11.10, 17.80)	14.80 (11.40, 19.40)	13.30 (11.00, 16.20)	<0.001
	DBIL, µmol/L	2.20 (1.70, 2.90)	2.60 (1.90, 3.40)	2.10 (1.60, 2.50)	<0.001
	IBIL, µmol/L	11.60 (9.50, 14.90)	12.40 (9.50, 15.40)	11.10 (9.40, 13.90)	0.013
Renal function indices	GFR, mL/min	104.45 (96.38, 112.99)	105.55 (96.51, 117.61)	103.54 (96.13, 109.22)	0.006
	Scr, µmol/L	61.10 (54.10, 69.70)	60.70 (53.10, 67.00)	61.50 (54.80, 73.00)	0.038
	SUA, µmol/L	317.70 (263.60, 392.60)	322.50 (271.30, 395.80)	312.30 (258.50, 388.50)	0.176
	BUN, g/L	4.90 (4.18, 5.87)	5.00 (4.20, 6.20)	4.70 (4.09, 5.59)	0.011
Biochemical indexes	TP, g/L	71.90 (68.20, 74.70)	70.40 (65.50, 74.70)	72.30 (70.00, 74.60)	<0.001
	ALB, g/L	43.70 (41.80, 45.30)	43.10 (40.20, 44.90)	44.20 (43.00, 45.70)	<0.001
	HB, g/L	144.00 (133.00, 155.00)	146.00 (134.00, 155.00)	142.00 (132.00, 155.00)	0.196
Electrolyte	K, mmol/L	4.00 (3.80, 4.30)	3.80 (3.60, 4.10)	4.10 (3.90, 4.40)	<0.001
	Na, mmol/L	140.00 (138.00, 141.00)	139.00 (137.00, 140.00)	140.00 (139.00, 141.00)	<0.001
	Ca, mmol/L	2.37 (2.30, 2.43)	2.33 (2.26, 2.41)	2.40 (2.34, 2.44)	<0.001
FBG, mmom/L		5.52 (5.04, 6.06)	5.88 (5.01, 6.93)	5.37 (5.05, 5.64)	<0.001
FA, ng/ml		8.46 (5.87, 12.83)	7.07 (5.20, 10.64)	10.10 (6.70, 14.26)	<0.001

Abbreviations: T2DM, type 2 diabetes mellitus; NC, normal control groups; BMI, body mass index; WC, waist circumference; BP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein- cholesterol; LDL-C, low-density lipoprotein-cholesterol; ApoB, Apolipoprotein B; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, glutamyltransferase; TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; GFR, glomerular filtration rate, Scr, serum creatinine; SUA, serum uric acid; TP, total albumin; ALB, serum albumin; HB, hemoglobin; FBG, fasting blood glucose; FINS, fasting serum insulin; FA, folic acid.

Table 2 Baseline Data of Patients with Type 2 Diabetes Mellitus in IR Group and Non-IR Group

Variables		Total (n=206)	IR (n=99)	Non-IR (n=107)	P-value
General physical indicators	Gender, male, n (%)	83 (40.29)	38 (38.38)	45 (42.06)	0.591
	Age, year	50.96 (±13.98)	51.40 (±12.91)	50.49 (±15.05)	0.642
	Height, cm	167.53 (±8.08)	167.83 (±8.46)	167.25 (±7.71)	0.606
	WC, cm	92.00 (85.00, 100.00)	94.00 (86.80, 102.00)	91.00 (84.00, 99.00)	0.034
	BMI, Kg/m^2	26.26 (23.84, 29.14)	27.55 (24.77, 30.08)	25.53 (23.26, 27.61)	<0.001
	SBP, mmHg	131.00 (120.00, 145.00)	132.00 (121.00, 146.00)	131.00 (116.00, 143.00)	0.313
	DBP, mmHg	83.29 (±12.38)	84.37 (±11.98)	82.29 (±12.67)	0.229
	Alcohol history, n (%)	38 (18.45)	16 (16.16)	22 (20.56)	0.416
	Smoking history, n (%)	45 (21.85)	25 (25.25)	20 (18.69)	0.255
	Diabetes duration years	4.00 (0.50, 10.00)	3.00 (0.30, 10.00)	4.00 (0.50, 11.00)	0.401
Blood lipid indices	TC, mmol/L	4.89 (4.02, 5.69)	4.84 (4.04, 5.55)	4.99 (3.95, 6.08)	0.446
	TG, mmol/L	1.65 (1.10, 2.63)	1.80 (1.21, 2.89)	1.47 (1.03, 2.39)	0.011
	HDL-C, mmol/L	1.04 (0.91, 1.23)	0.97 (0.87, 1.17)	1.11 (0.98, 1.30)	<0.001
	LDL-C, mmol/L	3.19 (2.62, 3.81)	3.18 (2.55, 3.77)	3.20 (2.62, 4.07)	0.280
	ApoB, g/L	0.93 (0.75, 1.12)	0.93 (0.73, 1.09)	0.95 (0.77, 1.13)	0.559
Hepatic function indices	AST, U/L	20.20 (16.50, 29.00)	21.00 (17.20, 31.50)	19.60 (15.90, 26.40)	0.045
	ALT, U/L	21.40 (15.00, 32.20)	22.90 (15.30, 38.20)	20.80 (14.40, 28.60)	0.094
	GGT, U/L	25.70 (18.60, 40.80)	24.30 (17.70, 34.80)	31.50 (19.10, 46.80)	0.043
	TBIL, umol/L	14.80 (11.40, 19.40)	14.70 (11.50, 19.60)	15.20 (11.20, 19.40)	0.775
	DBIL, umol/L	2.60 (1.90, 3.40)	2.60 (1.90, 3.40)	2.60 (1.90, 3.40)	0.903
	IBIL, umol/L	12.40 (9.50, 15.40)	12.00 (9.60, 15.40)	12.70 (9.30, 15.80)	0.706
Renal function indices	GFR, mL/min	105.55 (96.51, 117.61)	105.37 (96.47, 118.01)	105.98 (98.00, 117.61)	0.978
	Scr, umol/L	60.70 (53.10, 67.00)	61.60 (54.60, 68.30)	59.60 (49.40, 66.80)	0.260
	SUA, umol/L	322.50 (271.30, 395.80)	333.60 (275.50, 407.50)	307.80 (257.80, 387.80)	0.079
	BUN, g/L	5.00 (4.20, 6.20)	5.00 (4.40, 6.00)	5.000 (4.00, 6.30)	0.914
Biochemical indexes	TP, g/L	70.40 (65.50, 74.70)	70.70 (65.70, 76.00)	70.10 (65.00, 74.50)	0.556
	ALB, g/L	43.10 (40.20, 44.90)	43.30 (40.90, 45.10)	42.70 (39.60, 44.50)	0.241
	HB, g/L	144.84 (±17.22)	144.59 (±16.82)	145.07 (±17.58)	0.843
Electrolyte	K, mmol/L	3.80 (3.60, 4.10)	3.80 (3.60, 4.10)	3.90 (3.60, 4.20)	0.533
	Na, mmol/L	139.00 (137.00, 140.00)	139.00 (137.00, 140.00)	139.00 (137.00, 140.00)	0.996
	Ca, mmol/L	2.33 (2.26, 2.41)	2.34 (2.24, 2.410)	2.33 (2.28, 2.41)	0.718
Glucose metabolism indices	HOMA-IR,	1.67 (0.97, 2.85)	2.91 (2.29, 4.42)	1.01 (0.48, 1.35)	<0.001
	FBG, mmom/L	5.88 (5.01, 6.93)	6.47 (5.56, 7.66)	5.51 (4.74, 6.14)	<0.001
	FINS, pmol/L	6.36 (3.79, 9.86)	9.88 (7.84, 16.51)	3.84 (2.04, 5.18)	<0.001
	HbA1c, n (%)	9.60 (8.09, 11.10)	9.20 (7.50, 10.90)	10.30 (8.40, 11.60)	0.005
	FA, ngml	7.07 (5.20, 10.64)	5.92 (4.09, 9.02)	8.16 (6.33, 13.76)	<0.001

Abbreviations: IR, insulin resistance; Non-IR, Non insulin resistance; BMI, body mass index; WC, waist circumference; BP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-C, High density lipoprotein- cholesterol; LDL-C, Low density lipoprotein-cholesterol; ApoB, Apolipoprotein B; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, glutamyltransferase; TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; GFRglomerular filtration rate, Scr, serum creatinine; SUA, serum uric acid; TP, total albumin; ALB, serum albumin; HB, hemoglobin; HOMA-IR, homa insulin-resistance; FBG, fasting blood glucose; FINS, fasting serum insulin; HbA1c, glycated hemoglobin; FA, folic acid.

Table 3 Correlation Analysis Between Folic Acid and Other Indexes

Variables	r	P
WC	−0.143	0.040
BMI	−0.233	<0.001
Smoking history	−0.168	0.016
Alcohol history	−0.158	0.023
TG	−0.139	0.046
HDL-C	0.176	0.011
HB	−0.143	0.041
K	0.249	<0.001
Ca	0.171	0.014
Scr	−0.189	0.007
SUA	−0.198	0.004
FINS	−0.253	<0.001
HOMA-IR	−0.249	<0.001

Abbreviations: WC, waist circumference; BMI, body mass index; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; Scr, serum creatinine; SUA, serum uric acid; FINS, fasting serum insulin; HOMA-IR, homa insulin-resistance.

Table 4 Multivariate Logistic Regression Analysis of Insulin Resistance in Type 2 Diabetic Patients

Prameters	Crude Model		Model 1		Model 2
	P	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)
WC, cm	0.993	1.00 (0.94, 1.07)	0.825	1.01 (0.94, 1.08)	0.878	1.01 (0.94, 1.08)
BMI, kg/m^2	0.764	0.97 (0.80, 1.18)	0.437	0.93 (0.76, 1.13)	0.503	0.93 (0.76, 1.15)
FBG, mmom/L	<0.001	2.36 (1.60, 3.49)	<0.001	2.54 (1.64, 3.93)	<0.001	2.79 (1.76, 4.42)
FINS, pmol/L	<0.001	1.58 (1.34, 1.86)	<0.001	1.55 (1.32, 1.82)	<0.001	1.51 (1.29, 1.78)
HbA1c, %	0.101	0.85 (0.71, 1.03)	0.052	0.81 (0.65, 1.00)	0.126	0.84 (0.66, 1.05)
FA, ng/mL	0.017	0.86 (0.76, 0.97)	0.005	0.82 (0.72, 0.94)	0.003	0.81 (0.70, 0.93)
HDL-C, mmol/L	0.051	0.13 (0.02, 1.01)	0.024	0.08 (0.01, 0.71)	0.010	0.02 (0.00, 0.39)
TG, mmol/L	0.108	1.25 (0.95, 1.63)	0.118	1.24 (0.95, 1.62)	0.340	1.16 (0.86, 1.56)
AST, U/L	0.749	1.01 (0.96, 1.05)	0.841	1.01 (0.96, 1.05)	0.945	1.00 (0.95, 1.05)
ALT, U/L	0.676	1.02 (0.95, 1.09)	0.565	1.02 (0.95, 1.10)	0.488	1.03 (0.95, 1.11)
GGT, U/L	0.850	1.00 (0.99, 1.01)	0.726	1.00 (0.99, 1.02)	0.618	1.01 (0.99, 1.02)
BUN, g/L	0.270	1.00 (0.99, 1.00)	0.520	1.00 (0.99, 1.00)	0.380	1.00 (0.99, 1.00)

Notes: Crude Model: unadjusted; Model 1: adjusted for age, gender, duration diabetes, alcohol history, smoking history; Model 2: adjusted for Model 2 and total cholesterol, apolipoprotein B, albumin, hemoglobin, glomerular filtration rate.

Abbreviations: WC, waist circumference; BMI, body mass index; FBG, fasting blood glucose; FINS, fasting serum insulin; HbA1c, glycated hemoglobin; FA, folic acid; HDL-C, high-density lipoprotein cholesterol; TG, triglyceride; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, glutamyltransferase.

Table 5 Trend Test of Serum Folate Level for Risk of Insulin Resistance in Patients with Type 2 Diabetes Mellitus

Variables	Case	Control	Crude Model		Model 1		Model 2
			OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
Q1: 10.7125–54.37 ng/mL	12	39	1 (Ref)		1 (Ref)		1 (Ref)
Q2: 7.0900–10.7125 ng/mL	25	27	2.43 (0.64, 9.21)	0.192	2.73 (0.70, 10.62)	0.146	3.08 (0.72, 13.11)	0.129
Q3: 5.2000–7.0900 ng/mL	24	27	2.31 (0.58, 9.22)	0.236	3.62 (0.83, 15.86)	0.088	3.56 (0.73, 17.36)	0.116
Q4: 1.56–5.2000 ng/mL	38	14	6.17 (1.43, 26.73)	0.015	8.93 (1.81, 44.21)	0.007	11.88 (2.19, 64.46)	0.004
P for trend			P=0.114		P=0.064		P=0.041

Notes: Ref: reference; Crude Model: unadjusted; Model 1: adjusted for age, gender, duration diabetes, alcohol history, smoking history; Model 2: adjusted for Model 1 and total cholesterol, apolipoprotein B, albumin, hemoglobin, glomerular filtration rate.

Figure 1 (A–C) Cubic spline regression analysis of the relationship of serum folate levels and HOMA-IR, FBG, FINS in T2DM. The relationship between folate and (A) HOMA-IR, (B) FBG and (C) FINS using the cubic spline regression analyses. The regression curve is shown in red line and the shaded area represents the 95% confidence band. Age, sex, smoking history, drinking history and diabetes history were adjusted.

Abbreviations: HOMA-IR, insulin resistance was detected by the homeostasis model assessment method; FBG, fasting blood glucose; FINS, fasting insulin; T2DM, type 2 diabetes mellitus.