Clinical Features and Vitreous Biomarkers of Early-Onset Type 2 Diabetes Mellitus Complicated with Proliferative Diabetic Retinopathy

Figures & data

Figure 1 Flow chart of the study from recruiting participants to conducting analysis.

Table 1 Clinical Characteristics and Surgical Methods in the Early- and Late-Onset Groups

Clinical Characteristics	Early-Onset Group (n = 48)	Late-Onset Group (n = 38)	P-value
Age (years)	44.69 ± 8.51	57.76 ± 7.53	<0.001
Eyes (right, %)	23 (47.9%)	22 (57.9%)	0.358
Sex (male, %)	30 (62.5%)	17 (44.7%)	0.100
Age at DM diagnosis (years)	32.33 ± 5.18	47.84 ± 4.77	<0.001
Course of DM (years)	13.5 (7, 20)	10 (4.5, 15.75)	0.099
BMI (kg/m^2)	24.42 (22.73, 27.20)	23.45 (20.33, 23.45)	0.057
Family history of DM	23 (47.9%)	4 (10.5%)	<0.001
FBG (mmol/L)	7.76 (5.09, 10.61)	6.33 (5.05, 9.96)	0.256
HbA1c (%)	9.41 ± 2.28	7.61 ± 1.2	<0.001
TC (mmol/L)	5.12 ± 1.34	4.41 ± 1.03	0.009
e-GFR	74.90 (35.18, 103.93)	76.55 (55.75, 95.40)	0.774
Systolic blood pressure (mmHg)	143.92 ± 21.11	142.53 ± 20.13	0.758
Diastolic blood pressure (mmHg)	85.56 ± 11.30	82.71 ± 12.13	0.264
Pre-operative BCVA (LogMAR)	1.85 (1.6, 2.3)	1.85 (1.48, 2.3)	0.620
Pre-operative IOP (mmHg)	16.83 ± 3.84	15.95 ± 3.85	0.292
Preoperative DME	4 (8.3%)	2 (5.3%)	0.69
Iris neovascularization	2 (4.2%)	0 (0%)	0.501
Active FVP	37 (77.1%)	18 (47.4%)	0.004
Surgical indications			0.002
VH only	1 (2.1%)	11 (28.9%)
FVP with or without VH	31 (64.6%)	18 (47.4%)
TRD/TRRD with or without VH	16 (33.3%)	9 (23.7%)
Preoperative PRP (n, %)	22 (45.8%)	8 (21.1%)	0.017
Perioperative anti-VEGF (n, %)	34 (70.8%)	11 (28.9%)	<0.001
Cataract extraction (n, %)	7 (14.6%)	11 (28.9%)	0.104
Vitreous tamponade			0.599
BSS	13 (27.1%)	14 (36.8%)
Gas	22 (45.8%)	16 (42.1%)
Silicone oil	13 (27.1%)	8 (21.1%)

Abbreviations: BCVA, best corrected visual acuity; BMI, body mass index; DM, diabetes mellitus; FBG, fasting blood glucose; DME, diabetic macular oedema; FVP, fibrovascular proliferation; GFR, glomerular filtration rate; IOP, intraocular pressure; PRP, panretinal laser photocoagulation; TC, total cholesterol; TRD, tractional retinal detachment; TRRD, tractional rhegmatogenous retinal detachment; VH, vitreous haemorrhage; VEGF, vascular endothelial growth factor; BSS, balanced salt solution.

Figure 2 (A) Changes in BCVA in the early-onset and late-onset groups before operation and 1 months, 3 months, and 6 months after operation. (B) Postoperative complications in the two groups. *P < 0.05.

Table 2 Postoperative Complications in the Two Groups

Postoperative Complications	Early-Onset Group (n = 48)	Late-Onset Group (n = 38)	P-value
Recurrent VH	10 (20.8%)	2 (5.3%)	0.039
DME	7 (14.6%)	3 (7.9%)	0.534
Cataract	21 (43.8%)	12 (31.6%)	0.249
Recurrent RD	0 (0%)	2 (5.3%)	0.375
NVG	4 (8.3%)	1 (2.6%)	0.510

Abbreviations: DME, diabetic macular oedema; NVG, neovascular glaucoma; RD, retinal detachment; VH, vitreous haemorrhage.

Table 3 Vitreous Cytokine Levels in the Early- and Late-Onset Groups

Cytokine (pg/mL)	Early-Onset Group (n = 20)	Late-Onset Group (n = 16)	P-value
IL-1ra	373.97 (219.40, 692.88)	198.56 (103.26, 526.85)	0.053
IL-1β	0.50 (0.35, 0.68)	0.26 (0.19, 0.41)	0.011
IL-2	2.11 (1.53, 2.58)	1.07 (1.07, 1.53)	0.012
IL-4	0.70 (0.44, 1.02)	0.25 (0.21, 0.61)	0.002*
IL-6	142.21 (96.78, 353.30)	40.54 (20.33, 79.21)	<0.001*
IL-8	221.67 (132.33, 519.97)	58.59 (20.91, 116.83)	0.001*
IL-9	24.14 (9.23, 33.60)	3.27 (1.84, 8.02)	<0.001*
IL-10	1.90 (1.52, 3.53)	1.52 (1.17, 2.05)	0.386
IL-13	1.38 (0.78, 1.65)	1.2 (0.66, 1.74)	0.422
IL-17	3.01 (2.15, 4.06)	2.84 (1.80, 5.18)	0.838
G-CSF	113.71 (67.66, 178.64)	27.53 (20.42, 65.97)	<0.001*
IFN-γ	95.31 (53.47, 163.70)	34.37 (13.75, 51.60)	0.001*
IP-10	2583.5 (1870.25, 6421.75)	595.67 (361.26, 1163.75)	<0.001*
MCP-1	1268.0 (979.03, 1509.25)	613.89 (308.81, 962.31)	<0.001*
MIP-1α	2.33 (1.47, 3.75)	0.76 (0.49, 1.62)	<0.001*
MIP-1β	21.51 (14.81, 33.85)	5.87 (3.29, 12.05)	<0.001*
RANTES	7.66 (6.14, 11.38)	5.88 (2.92, 11.20)	0.211
TNF-α	6.43 (4.76, 10.36)	4.36 (2.44, 9.03)	0.178
VEGF	110.48 (37.16, 200.94)	33.94 (13.14, 117.68)	0.036

Note: *A Bonferroni correction was adopted with significance set for a P-value less than 0.0026.

Abbreviations: G-CSF, granulocyte colony-stimulating factor; IFN-γ, interferon-γ; IL, interleukin; IL-1ra, IL-1 receptor antagonist; IP-10, interferon-inducible 10 kDa protein; MCP-1, monocyte chemotactic protein 1; MIP, macrophage inflammatory protein; RANTES, regulated upon activation, normal T cell expressed and secreted; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor.

Figure 3 A heatmap of correlation coefficients between cytokine concentrations and clinical characteristics. Dark blue denotes high correlation (R→1); deep red, high negative correlation (R→−1); and white, a lack of correlation (R→0). An R value of 0.3 was set as the threshold and P < 0.05 was considered significant.

Abbreviations: DM, diabetes mellitus; Pre.OP, preoperative; DM age, age at diagnosis of DM; BCVA, best corrected visual acuity; Post.OP BCVA, postoperative BCVA at last follow-up; DME, diabetic macular oedema; NVG, neovascular glaucoma; RD, retinal detachment; VH, vitreous haemorrhage; G-CSF, granulocyte colony-stimulating factor; HbA1c, haemoglobin A1c; IFN-γ, interferon-γ; IL, interleukin; IL-1ra, IL-1 receptor antagonist; IP-10, interferon-inducible 10 kDa protein; MCP-1, monocyte chemotactic protein 1; MIP, macrophage inflammatory protein; RANTES, regulated upon activation, normal T cell expressed and secreted; TNF-α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor.

Table 4 Stepwise Multivariate Linear Regression Analysis of Risk Factors for Visual Prognosis (the BCVA at 6 Months After Operation) of PDR

Variables	Unstandardized Coefficients		Standardized Coefficients	P-value
	β	Std. Error	β
Age at DM diagnosis	−0.028	0.008	−0.385	0.002
HbA1C	0.110	0.033	0.383	0.002
IL-4	0.355	0.094	0.387	0.001
RANTES	0.004	0.001	0.307	0.006

Abbreviations: HbA1c, haemoglobin A1c; IL, interleukin; RANTES, regulated upon activation, normal T cell expressed and secreted; BCVA, best corrected visual acuity; PDR, proliferative diabetic retinopathy.