Factors associated with development of retinopathy in patients with type 2 diabetes mellitus at onset and within three years after diagnosis

Figures & data

Table 1. Basic of characteristics at index.

	No DR, n (%)	DR, n (%)	Total, n (%)	p-value
Total cohort	1129 (69)	530 (32)	1659 (100)
Age, (years)
< 60	477 (42)	222 (42)	699 (42)	0.89
> 60	652 (58)	308 (58)	960 (58)
Gender
Men	691 (61)	340 (64)	1031 (62)	0.25
Women	438 (39)	190 (36)	628 (38)
Comorbidities
Hypertension	576 (51)	275 (52)	851 (51)	0.74
ASCVD	164 (14)	70 (13)	239 (14)	0.47
IHD	125 (11)	50 (9)	175 (10)	0.31
Ischemic CVI	30 (3)	14 (3)	44 (3)	0.98
TIA	18 (2)	10 (2)	28 (2)	0.67
PAD	0 (0)	2 (0)	2 (0)	0.04
Heart Failure	41 (4)	24 (4)	65 (4)	0.38
HbA1c (mmol/mol)
<52	442 (40)	123 (23)	565 (34)	<0.001
52–57	215 (19)	80 (15)	295 (18)
58–70	178 (16)	119 (22)	297 (18)
>70	294 (26)	208 (39)	502 (30)
Cholesterol (mmol/l)
<4.5	328 (29)	147 (28)	475 (29)	0.10
>4.5	748 (66)	369 (70)	1117 (67)
Missing value	53 (5)	14 (3)	67 (4)
LDL (mmol/l)
<2.5	253 (22)	129 (24)	382 (23)	0.04
>2.5	816 (72)	387 (73)	1203 (72)
Missing value	60 (5)	14 (3)	74 (4)
Kidney function (eGFR)
>60 mL/min/1.73^2	915 (81)	395 (74)	1310 (79)	0.003
31-59 mL/min/1.73^2	111 (10)	85 (16)	196 (12)
<30 mL/min/1.73^2	14 (1)	8 (2)	22 (1)
Missing value	89 (8)	42 (8)	131 (8)
Proteinuria (UACR), n (%)
<3	344 (30)	156 (29)	500 (30)	0.04
3–29	126 (11)	86 (16)	212 (13)
>30	37 (3)	14 (3)	51 (3)
Missing value	622 (55)	274 (52)	896 (54)
Blood pressure (systolic)
<130 mmHg	424 (38)	120 (23)	544 (33)	<0.001
130–140 mmHg	157 (14)	95 (18)	252 (15)
>140 mmHg	536 (48)	315 (59)	851 (51)
Missing value	12 (1)	0 (0)	12 (1)

Note; DR: diabetes retinopathy; ASCVD: atherosclerotic cardiovascular disease; eGFR: estimated glomerular filtration rate; UACR: urine albumin creatinine ratio.

Table 2. The characteristics after three years from index.

	No DR, n (%)	DR, n (%)	Total, n (%)	p-value
HbA1c (mmol/mol)
<52	511 (45)	199 (38)	710 (43)	<0.001
52-57	225 (20)	113 (21)	338 (20)
58-70	163 (14)	111 (21)	274 (17)
>70	95 (8)	92 (17)	187 (11)
Missing value	135 (12)	15 (3)	150 (9)
Cholesterol (mmol/l)
<4.5	439 (39)	210 (40)	649 (39)	<0.001
>4.5	480 (43)	279 (53)	759 (46)
Missing value	210 (19)	41 (8)	251 (15)
LDL-cholesterol (mmol/l)
<2.5	398 (35)	197 (37)	595 (36)	<0.001
>2.5	561 (50)	311 (59)	872 (53)
Missing value	170 (15)	22 (4)	192 (12)
Kidney function (eGFR)
>60 mL/min/1.73^2	539 (48)	245 (46)	784 (47)	0.007
31–59 mL/min/1.73^2	132 (12)	92 (17)	224 (14)
<30 mL/min/1.73^2	23 (2)	19 (4)	42 (2)
Missing value	435 (38)	174 (33)	609 (37)
Blood pressure (systolic)
<130 mm Hg	474 (42)	121 (23)	595 (36)	<0.001
130–140 mm Hg	203 (18)	104 (20)	307 (19)
>140 mm Hg	396 (35)	299 (56)	695 (42)
Missing value	56 (5)	6 (1)	62 (4)
Visiting an ophthalmologist, n (%)	776 (68)	411 (78)	1177 (71)	<0.001

Note; DR: diabetes retinopathy; HbA1c:hemoglobin A1c; LDL-cholesterol: low-density lipoprotein; eGFR: estimated glomerular filtration rate.

Table 3. Shows the pharmacotherapeutic treatment during the study period in total and divided between the patients with diabetes retinopathy and those without.

	No DR	DR	Total	p-value
Diabetes pharmacotherapy
Dietary treatment, n (%)	114 (10)	25 (5)	139 (8)	<0.001
Metformin, n (%)	946 (84)	463 (87)	1409 (85)	0.06
SU, n (%)	13 (1)	15 (3)	28 (2)	0.01
GLP-1, n (%)	141 (12)	94 (18)	235 (14)	0.003
Insulin, n (%)	153 (14)	112 (21)	265 (16)	<0.001
DPP4, n (%)	181 (16)	112 (21)	293 (18)	0.01
SGLT-2, n (%)	85 (8)	74 (14)	159 (10)	<0.001
Lipid-lowering pharmacotherapy
Statins, n (%)	682 (60)	346 (65)	1028 (62)	0.06
Ezetimibe, n (%)	34 (3)	23 (4)	57 (3)	0.17
Cardiovascular pharmacotherapy
Betablockers, n (%)	434 (38)	206 (39)	640 (39)	0.87
RAASi, n (%)	668 (59)	357 (67)	1025 (62)	0.001
Calcium-blockers, n (%)	362 (32)	199 (38)	561 (34)	0.03

Note; DR = diabetes retinopathy, SU = Sulphonylureas, GLP-1= Glucagon-like peptide-1 receptor agonist, Insulin = includes fast-acting, intermediate-acting, intermediate-acting combined with fast acting or long-acting insulin, DPP4= Dipeptidyl peptidase 4 inhibitors, SGLT-2 = Sodium glucose co-transporter-2 inhibitors, RAASi = renin angiotensin aldosterone system inhibitors (including angiotensin converting enzyme inhibitors, angiotensin receptor blockers and angiotensin receptor neprilysin inhibitors).

Table 4. Presents the risk of developing diabetes retinopathy adjusted for glucose, cholesterol and blood pressure control as well as kidney function at index and at three years from onset.

	At onset (n = 1459)				Within three years from diagnosis (n = 940)
	Odds ratio	95% CI for odds ratio		p-value	Odds ratio	95% CI for odds ratio		p-value
		Lower	Upper			Lower	Upper
Age	0.99	0.98	1.01	0.39	0.99	0.97	1.00	0.17
Women	0.90	0.71	1.14	0.39	0.98	0.72	1.32	0.88
Hypertension	0.96	0.75	1.24	0.76	0.92	0.68	1.24	0.59
ASCVD	0.94	0.63	1.27	0.71	0.94	0.62	1.43	0.78
HbA1c				<0.001				<0.001
<52 mmol/mol	Reference				Reference
52-57 mmol/mol	1.31	0.92	1.87		1.39	0.95	2.02
58-70 mmol/mol	2.23	1.58	3.15		2.01	1.37	2.95
>70 mmol/mol	2.60	1.92	3.50		2.17	1.41	3.34
Lipids
Cholesterol >4,5	0.94	0.73	1.73	0.71	0,98	0,64	1,50	0.91
Kidney function				<0.001				0.003
>60 ml/min	Reference				Reference
30-59 ml/min	2.02	1.43	2.84		1.75	1.22	2.51
<30 ml/min	1.98	0.75	5.21		2.17	1.03	4.56
Blood pressures				<0.001				<0.001
<130 mm Hg	Reference				Reference
131-139 mm Hg	2.34	1.63	3.36		2.23	1.48	3.37
>140 mm Hg	2.12	1.62	2.85		3.93	2.80	5.51

Note: CI: confidence interval; ASCVD: atherosclerotic cardiovascular disease, HbA1c: hemoglobin A1c; LDL-cholesterol: low density lipoprotein cholesterol.