Lower Visceral Fat Area in Patients with Type 2 Diabetic Peripheral Neuropathy

Figures & data

Figure 1 Flow chart of the selection of study participants.

Table 1 Clinical and Biochemical Characteristics of Patients Stratified by Presence of DPN

Variables	Non-DPN (n=1594)	DPN (n=900)	P-value
Male/Female	837/757	480/420	0.692
Age (years)	56.69±10.99	54.32±11.55	<0.001
BMI (kg/m2)	25.0±3.4	24.1±3.6	<0.001
VFA(cm2)	88.88±42.72	71.53± 44.40	<0.001
Diabetic duration (years)	7.94±5.99	9.47± 6.79	<0.001
FBG (mmol/L)	9.39±3.23	10.26± 3.54	<0.001
2hPBG (mmol/L)	14.43±4.65	15.55± 5.12	<0.001
HbA1c (%)	9.44±2.49	10.49±2.53	<0.001
FCP (ng/mL)	1.98±1.52	1.60±1.40	<0.001
HOMA-IR	3.55±2.01	3.39±1.82	0.044
TyG index	9.50±0.78	9.55±0.78	0.062
SBP (mmHg)	133.79±19.08	138.17±23.19	<0.001
DBP (mmHg)	78.58±10.79	80.97±11.93	<0.001
PP (mmHg)	55.22±13.53	57.20±15.54	0.009
TC (mmol/L)	4.77±2.22	4.89± 1.61	0.145
TG (mmol/L)	2.45±2.46	2.36± 2.32	0.183
HDL-C (mmol/L)	1.14±0.33	1.18± 0.40	0.026
LDL-C (mmol/L)	2.80±1.02	2.89± 1.17	0.180
WBC (*10^9/L)	6.80±2.13	7.11±2.43	0.004
RBC (*10^12/L)	4.65±0.59	4.48±0.71	<0.001
Hb (g/L)	139.00±17.61	132.31±22.12	<0.001
TBIL (μmol/L)	13.48±5.82	12.39±7.29	<0.001
GGT (U/L)	43.11±75.22	49.09±156.72	0.075
Serum albumin (g/L)	44.40±4.36	42.68±5.41	<0.001
Serum UA (μmol/L)	350.22±468.46	341.40±183.74	0.645
Urine ACR (mg/g)	124.67±530.92	440.02± 1141.27	<0.001
Serum Cr (μmol/L)	65.14±26.36	75.10±59.98	0.366
eGFR (mL/min/1.73m2)	98.61±20.24	96.72±28.34	0.218
AC	3.47±2.91	3.44±2.12	0.862
AIP	0.55±0.81	0.49±0.82	0.093
ABI	1.10±0.09	1.09±0.11	0.068
SNCV (m/s)	54.97±4.02	46.32± 5.63	<0.001
SNAP (μV)	15.87±7.23	8.56± 5.71	<0.001
Microvascular complications
DN (n, %)	440 (27.60%)	408 (45.33%)	<0.001
DR (n, %)	205 (12.86%)	280 (31.11%)	<0.001
Macrovascular complications
Hypertension (n, %)	612 (38.39%)	284 (31.56%)	0.001
CHD (n, %)	89 (5.58%)	37 (4.11%)	0.106
Stroke (n, %)	81 (5.08%)	39 (4.33%)	0.402
DFU (n, %)	12 (0.75%)	33 (3.67%)	<0.001
PAD (n, %)	36 (2.26%)	41 (4.56%)	0.001
Hypoglycemic drugs
Metformin (n, %)	843 (52.89%)	419 (46.56%)	0.002
Sulfonylurea (n, %)	443 (27.79%)	251 (27.89%)	0.959
Alpha-glucosidase inhibitor (n, %)	195 (12.23%)	91 (10.11%)	0.110
DPP-4 inhibitors (n, %)	69 (4.33%)	24 (2.67%)	0.035
SGLT-2 inhibitors (n, %)	15 (0.94%)	11 (1.22%)	0.507
Other oral agents (n, %)	304 (19.07%)	148 (16.44%)	0.102
Insulin (n, %)	457 (28.67%)	374 (41.56%)	<0.001
Antihypertensive drugs
ACEI/ARB (n, %)	215 (13.49%)	59 (6.56%)	<0.001
Alcium antagonist (n, %)	239 (14.99%)	90 (10.00%)	<0.001
Others (n, %)	45 (2.82%)	18 (2.00%)	0.208
Antihyperlipidemic drugs (n, %)	89 (5.58%)	36 (4.00%)	0.082
Antiplatelet drugs (n, %)	22 (1.38%)	6 (0.67%)	0.104
Smoking (n, %)	332 (20.83%)	205 (22.78%)	0.116
Fresh vegetable intake
≥ 600 g/d (n, %)	249 (15.62%)	124 (13.78%)	0.208
<600 g/d (n, %)	1345 (84.38%)	776 (86.22%)
Fresh fruit intake
≥ 200 g/d (n, %)	391 (24.53%)	163 (18.11%)	<0.001
<200 g/d (n, %)	1203 (75.47%)	737 (81.89%)
Soy consumption
≥ 100 g/d (n, %)	234 (14.68%)	81 (9.00%)	<0.001
<100 g/d (n, %)	1360 (85.32%)	819 (91.00%)
Fish intake
≥ two times/week (n, %)	241 (15.12%)	82 (9.11%)	<0.001
≤ one time/week (n, %)	1353 (84.88%)	818 (90.89%)

Note: Values are presented as number (percentages) or mean± standard deviation).

Abbreviations: DPN, diabetic peripheral neuropathy; BMI, body mass index; VFA, visceral fat area; FBG, fasting blood glucose; 2hPBG, 2h postprandial blood glucose; HbA1c, glycated hemoglobin A1c; FCP, fasting C-peptide; HOMA-IR, homeostasis model assessment of insulin resistance; TyG index, triglyceride-glucose index; SBP, systolic blood pressure; DBP, diastolic blood pressure; PP, pulse pressure; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; WBC, white blood cell; RBC, red blood cell; Hb, hemoglobin; TBIL, total bilirubin; GGT, gamma glutamyltransferase; UA, uric acid; ACR, albumin-to-creatinine ratio;Cr, creatinine; eGFR, estimated glomerular filtration rate; AC, atherogenic coefficient; AIP, atherogenic index of plasma; ABI, ankle-brachial index; SNCV, sural nerve conduction velocity; SNAP, sural nerve amplitude potential; DN, diabetic nephropathy; DR, diabetic retinopathy; CHD, coronary heart disease; DFU, diabetic foot ulceration; PAD, peripheral arterial disease; DPP-4, dipeptidyl peptidase-4; SGLT-2, sodium-glucose cotransporter-2; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blocker.

Figure 2 Comparison of VFA levels between non-DPN and DPN groups. *P < 0.01 vs non-DPN group.

Table 2 Relationship Between VFA and Risk Factors Associated with DPN in Study Participants

Variables	r	P‑value	Adjusted r	Adjusted P‑value
Gender	−0.070	<0.001
Age	0.157	<0.001
BMI	0.712	<0.001
Diabetic duration	0.053	0.022
FBG	0.014	0.490	−0.069	0.362
2hPBG	0.013	0.542	−0.095	0.206
HbA1c	−0.117	<0.001	−0.190	0.011
FCP	0.370	<0.001	0.160	0.033
HOMA-IR	0.321	<0.001	0.111	0.001
TyG index	0.279	<0.001	0.171	<0.001
SBP	0.206	<0.001	0.073	0.334
DBP	0. 209	<0.001	0.016	0.832
PP	0.123	<0.001	−0.033	0.320
TC	0.017	0.410	0.056	0.455
TG	0.335	<0.001	0.146	0.051
HDL-C	−0.222	<0.001	−0.011	0.888
LDL-C	−0.023	0.263	−0.061	0.419
WBC	0.085	<0.001	−0.042	0.575
RBC	0.164	<0.001	0.020	0.788
Hb	0.182	<0.001	0.145	0.053
TBIL	0.102	<0.001	0.025	0.742
GGT	0.257	<0.001	0.128	0.088
Serum albumin	0.141	<0.001	0.133	0.075
Serum UA	0.246	<0.001	0.195	0.009
Urine ACR	0.038	0.082	0.045	0.546
Serum Cr	0.143	<0.001	0.134	0.073
eGFR	−0.149	<0.001	−0.007	0.839
AC	0.211	<0.001	0.065	0.046
AIP	0.343	<0.001	0.176	<0.001
ABI	0.007	0.719	−0.019	0.422
SNCV	0.129	<0.001	0.123	<0.001
SNAP	0.174	<0.001	0.170	<0.001
DPN	−0.201	<0.001	−0.144	<0.001
Hypertension	0.244	<0.001	0.070	0.003
CHD	0.060	0.003	−0.032	0.174
Stroke	0.019	0.352	−0.042	0.072
DFU	−0.027	0.184	0.026	0.259
PAD	0.029	0.152	0.008	0.716
DN	0.036	0.071	−0.020	0.387
DR	−0.060	0.003	−0.049	0.034
Hypoglycemic medication	0.017	0.402	−0.009	0.718
Antihypertensive drugs	0.221	0.000	0.073	0.002
Antihyperlipidemic drugs	0.080	0.000	0.080	0.001
Antiplatelet drugs	0.008	0.690	−0.017	0.489
Smoking	0.040	0.056	0.042	0.080
Fresh vegetable intake	0.060	0.003	0.083	0.001
Fresh fruit intake	0.022	0.283	−0.009	0.695
Soy consumption	0.002	0.915	−0.036	0.136
Fish intake	0.046	0.023	0.025	0.293

Table 3 OR and 95% CI of the Risk of DPN According to VFA Quartiles

VFA	DPN
	Model 1	Model 2	Model 3	Model 4	Model 5
	OR(95% CI)	OR(95% CI)	OR(95% CI)	OR(95% CI)	OR(95% CI)
Per SD increase	0.639 (0.582–0.702)	0.596 (0.509–0.698)	0.572 (0.457–0.716)	0.477 (0.340–0.671)	0.467 (0.336–0.649)
Quartiles of VFA
Q1 (≤54 cm2)	1	1	1	1	1
Q2 (55–79 cm2)	0.352 (0.276–0.449)	0.424 (0.313–0.574)	0.376 (0.242–0.586)	0.576 (0.310–1.072)	0.562 (0.305–1.037)
Q2 (80–107 cm2)	0.401 (0.318–0.506)	0.501 (0.355–0.708)	0.444 (0.270–0.729)	0.480 (0.227–1.014)	0.452 (0.217–0.941)
Q4 (≥108 cm2)	0.346 (0.273–0.437)	0.399 (0.261–0.608)	0.387 (0.212–0.707)	0.382 (0.151–0.968)	0.341 (0.137–0.847)
P for trend	<0.001	<0.001	<0.001	0.001	<0.001
Q4 versus. Q1, Q2, Q3	<0.001	<0.001	<0.001	0.020	0.039

Notes: Data are expressed as OR (95% CI) +P value, unless stated otherwise. Model 1 unadjusted; Model 2 adjusted for age, gender, BMI and diabetic duration; Model 3 adjusted for factors listed in Model 2 plus SBP, DBP, FBG, 2hPBG, FCP, HbA1c, TC, TG, HDL-C, LDL-C, HOMA-IR, TyG; Model 4 adjusted for factors listed in Model 3 plus HB, RBC, WBC, TBIL, GGT, serum albumin, UA, CHD, Stroke, DFU, PAD, DN, DR, AIP, AC; Model 5 adjusted for factors listed in Model 4 plus medication status (hypoglycemic medication, antihypertensive drugs, antihyperlipidemic drugs, and antiplatelet drugs), smoking, fresh vegetable intake, fresh fruit intake, soy consumption, and fish intake.

Abbreviations: OR, odds ratio; CI, confidence interval.

Table 4 The Result of Two-Piecewise Linear Regression Model

	OR (95% CI)	P value
Fitting model by standard linear regression	0.982(0.974–0.990)	<0.001
Fitting model by two-piecewise linear regression
Inflection point of VFA (cm2)	104	–
< 104	0.980(0.970–0.989)	<0.001
≥ 104	0.989(0.974–1.004)	0.150
P for log likelihood ratio test	–	0.344

Notes: We adjusted parameters such as anthropometry, glucolipid metabolism, inflammation, oxidative stress, diabetic vasculopathy, medication status, smoking, fresh vegetable intake, fresh fruit intake, soy consumption, and fish intake.

Abbreviations: OR, odds ratio; CI, confidence interval.

Figure 3 Multivariate adjusted smoothing spline plots of the Risk of DPN hospitalized patients with T2DM. We adjusted parameters such as anthropometry, glucolipid metabolism, inflammation, oxidative stress, and diabetic vasculopathy in Model 5 of Table 3. The solid red line represents the best-fit line, and the dotted blue lines are 95% confidence intervals.

Figure 4 ROC analysis of visceral fat area (VFA) to predict the presence of DPN in T2DM patients. AUC = 0.621; 95% CI, 0.597–0.644; P<0.001; identified VFA cutoff value = 50.5 cm²; Youden index = 0.184; sensitivity: 84.40%; specificity: 34.00%.