Pentosidine levels in nonproteinuric diabetes associated with both low estimated glomerular filtration rate and cataract

Figures & data

Table 1 Patient characteristics according to the presence or absence of low estimated glomerular filtration rate

	Case	Control	P value
n (%)	125 (14.1)	763 (85.9)
Male, n (%)	55 (44.0)	341 (44.7)	0.885
Age (yrs)	70.8 (8.8)	62.1 (9.2)	<0.0001
Median diabetes duration (years)	6 (0–42)	7 (0–48)	0.653
BMI (kg/m^2)	25.1 (3.4)	24.8 (3.7)	0.372
WHR	0.90 (0.07)	0.89 (0.07)	0.017
HbA1c (%)	7.3 (0.9)	7.3 (1.0)	0.909
HbA1c (mmol/mol)	56.0 (9.9)	56.0 (11.2)	0.909
Systolic blood pressure (mmHg)	136 (14)	133 (13)	0.007
Diastolic blood pressure (mmHg)	76 (9)	77 (8)	0.076
Mean arterial pressure (mmHg)	96 (9)	96 (7)	0.758
Serum creatinine (μmol/L)	113.7 (20.5)	74.2 (16.5)	<0.0001
Triacylglycerol (mmol/L)	1.58 (0.70)	1.37 (0.74)	0.004
Total cholesterol (mmol/L)	4.70 (0.77)	4.72 (0.80)	0.890
LDL cholesterol (mmol/L)	2.72 (0.63)	2.81 (0.68)	0.201
HDL cholesterol (mmol/L)	1.28 (0.34)	1.29 (0.33)	0.802
Smoking, n (%)
Current	10 (8.0)	66 (8.7)	0.607
Never	90 (72.0)	571 (74.9)
Former	25 (20.0)	125 (16.4)
Patients on antihypertensive drugs, n (%)
1 drug	36 (29.5)	267 (35.9)	<0.001
2 drug	43 (35.3)	205 (27.6)
3 or more drugs	36 (29.5)	111 (14.9)
Not on medication	7 (5.7)	160 (21.5)
Patients on lipid-lowering drugs, n (%)
1 drug	86 (71.7)	596 (80.2)	0.177
2 drug	11 (9.2)	44 (5.9)
3 or more drugs	0 (0.0)	1 (0.1)
Not on medication	23 (19.2)	102 (13.7)
Treatment for diabetes, n (%)
Diet/exercise alone	33 (27.1)	179 (24.0)	0.556
Oral hypoglycemic drugs alone	78 (63.9)	520 (69.6)
Oral hypoglycemic drugs with insulin	10 (8.2)	45 (6.0)
Insulin	1 (0.8)	3 (0.4)
History of diabetic retinopathy, n (%)
None	87 (77.7)	589 (84.0)	0.096
Any retinopathy	25 (22.3)	112 (16.0)
History of coronary artery disease, n (%)
Yes	19 (15.2)	98 (12.8)	0.470
No	106 (84.8)	665 (87.2)
History of cerebrovascular disease, n (%)
Yes	14 (11.2)	44 (5.8)	0.023
No	111 (88.8)	719 (94.2)
History of cataract, n (%)
Yes	54 (43.2)	188 (24.6)	<0.001
No	71 (56.8)	575 (75.4)

Note: Values are the mean (SD) unless stated otherwise.

Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; WHR, waist-hip ratio; HbA_1c, Hemoglobin A_1c; LDL, low-density lipoprotein; HDL, high-density lipoprotein; SD, standard deviation.

Table 2 Multivariate association between cataract and low estimated glomerular filtration rate, adjusted for hypertension and triacylglycerola

Variable	OR (95% CI)	P value
Model 1 (without age in the model)
Cataract	2.50 (1.69–3.71)	<0.001
Hypertension	3.49 (1.59–7.70)	0.002
Triacylglycerol	1.36 (1.08–1.73)	0.010
Model 2 (with age in the model)
Cataract	1.16 (0.75–1.81)	0.509
Hypertension	2.97 (1.32–6.72)	0.009
Triacylglycerol	1.46 (1.14–1.87)	0.003
Age	1.11 (1.08–1.14)	<0.001

Notes:

a Apart from cataract, only covariates (hypertension and triacylglycerol) which were statistically significant in the final model are shown. Adjustment for age is included in Model 2.

Abbreviations: eGFR, estimated glomerular filtration rate; OR, odds ratio; CI, confidence interval.

Table 3 Patient characteristics and plasma pentosidine levels according to the presence of low estimated glomerular filtration rate and history of cataract

	Group 1	Group 2	Group 3	Group 4	P value
Low eGFR	No	Yes	No	Yes
History of cataract	Yes	Yes	No	No
n (%)	48 (25.5)	44 (23.4)	48 (25.5)	48 (25.5)
Male, n (%)	17 (35.4)	21 (47.7)	14 (29.2)	21 (43.8)	0.253
Age (years)	68.2 (7.1)	73.6 (6.7)	61.2 (9.4)	68.6 (8.9)	<0.0001
Median diabetes duration (years)	8 (0–48)	6 (0–27)	7 (0–32)	5 (0–42)	0.882
BMI (kg/m^2)	24.6 (3.7)	25.1 (3.5)	24.8 (3.7)	25.0 (3.6)	0.907
WHR	0.90 (0.08)	0.91 (0.08)	0.87 (0.06)	0.90 (0.06)	0.060
HbA1c (%)	7.5 (1.3)	7.1 (0.7)	7.1 (0.7)	7.4 (1.0)	0.051
HbA1c (mmol/mol)	58.3 (13.8)	54.1 (8.4)	53.8 (7.3)	57.4 (10.5)	0.051
Systolic blood pressure (mmHg)	133 (9.0)	137 (15)	133 (12)	137 (15)	0.249
Diastolic blood pressure (mmHg)	77 (6)	77 (9)	76 (7)	75 (9)	0.554
Mean arterial pressure (mmHg)	96 (6)	97 (9)	95 (6)	96 (9)	0.863
Serum creatinine (μmol/L)	74.9 (15.8)	110.7 (15.9)	74.6 (16.4)	115.1 (23.0)	<0.0001
Triacylglycerols (mmol/L)	1.52 (1.19)	1.53 (0.64)	1.40 (0.51)	1.64 (0.78)	0.570
Total cholesterol (mmol/L)	4.87 (0.83)	4.73 (0.78)	4.69 (0.88)	4.69 (0.84)	0.656
LDL cholesterol (mmol/L)	2.87 (0.73)	2.79 (0.63)	2.77 (0.76)	2.68 (0.69)	0.632
HDL cholesterol (mmol/L)	1.40 (0.36)	1.26 (0.29)	1.28 (0.30)	1.26 (0.29)	0.099
Smoking, n (%)
Current	2 (4.2)	4 (9.1)	3 (6.3)	6 (12.5)	0.699
Never	36 (75.0)	30 (68.2)	38 (79.2)	34 (70.8)
Former	10 (20.8)	10 (22.7)	7 (14.6)	8 (16.7)
Patients on antihypertensive drugs, n (%)
1 drug	10 (21.7)	12 (27.3)	15 (34.9)	18 (38.3)	0.045
2 drug	19 (41.3)	15 (34.1)	10 (23.3)	15 (31.9)
3 or more drugs	9 (19.6)	14 (31.8)	8 (18.6)	13 (27.7)
Not on medication	8 (17.4)	3 (6.8)	10 (23.3)	1 (2.1)
Patients on lipid-lowering drugs, n (%)
1 drug	34 (73.9)	32 (72.7)	36 (83.7)	32 (71.1)	0.518
2 drug	4 (8.7)	2 (4.6)	3 (7.0)	6 (13.3)
3 or more drugs	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Not on medication	8 (17.4)	10 (22.7)	4 (9.3)	7 (15.6)
Treatment for diabetes, n (%)
Diet/exercise alone	14 (29.8)	12 (27.3)	9 (20.9)	13 (27.7)	0.477
Oral hypoglycemic drugs alone	29 (61.7)	30 (68.2)	33 (76.7)	28 (59.6)
Oral hypoglycemic drugs with insulin	2 (4.3)	2 (4.6)	1 (2.3)	5 (10.6)
Insulin	2 (4.3)	0 (0.0)	0 (0.0)	1 (2.1)
Diabetic retinopathy, n (%)
None	39 (83.0)	30 (69.8)	39 (90.7)	31 (75.6)	0.085
Any retinopathy	8 (17.0)	13 (30.2)	4 (9.3)	10 (24.4)
History of coronary artery disease, n (%)
Yes	40 (83.3)	35 (79.6)	44 (91.7)	42 (87.5)	0.378
No	8 (16.7)	9 (20.5)	4 (8.3)	6 (12.5)
History of cerebrovascular disease, n (%)
Yes	6 (12.5)	8 (18.2)	4 (8.3)	3 (6.3)	0.281
No	42 (87.5)	36 (81.8)	44 (91.7)	45 (93.8)
eGFR, mL/min/1.73 m^2	82.7 (16.9)	52.3 (4.8)	83.3 (15.8)	51.0 (7.5)	<0.001
Pentosidine, ng/mL	173 (22–1147)	313 (2–1342)	166 (16–1846)	150 (28–1416)	0.036

Note: Values are the mean (SD) unless stated otherwise.

Abbreviations: eGFR, estimated glomerular filtration rate; BMI, body mass index; WHR, waist-hip ratio; HbA_1c, Hemoglobin A_1c; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

Table 4 Multivariate analysis of the joint phenotype of low estimated glomerular filtration rate and history of cataract with plasma pentosidine levels as a binary variablea

	Group 1b	Group 2b	Group 4b
Low eGFR	No	Yes	Yes
History of cataract	Yes	Yes	No
RR (95% CI)	RR (95% CI)	RR (95% CI)
Model 1 (without age in the model)
Pentosidine	0.98 (0.40–2.36)	4.43 (1.69–11.66)	1.03 (0.40–2.62)
HbA1c	1.53 (0.93–2.52)	0.67 (0.37–1.24)	1.26 (0.74–2.13)
Hypertension	1.33 (0.44–4.04)	10.27 (1.82–58.05)	12.33 (1.41–107.54)
Diabetic retinopathy	1.77 (0.47–6.61)	6.73 (1.76–25.71)	3.55 (0.94–13.47)
Model 2 (with age in the model)
Pentosidine	0.85 (0.33–2.15)	3.90 (1.29–11.78)	0.89 (0.33–2.34)
Age	1.12 (1.06–1.19)	1.25 (1.15–1.36)	1.09 (1.02–1.16)
HbA1c	1.84 (1.06–3.18)	0.76 (0.37–1.55)	1.44 (0.82–2.54)
Hypertension	1.01 (0.31–3.28)	4.97 (0.80–30.85)	10.44 (1.17–93.12)
Diabetic retinopathy	2.05 (0.49–8.59)	7.85 (1.70–36.27)	4.03 (0.95–17.13)

Notes:

a Apart from pentosidine, only covariates (HbA_1c, history of hypertension and diabetic retinopathy) which were statistically significant in the final model are shown;

b group 3 is the referent category.

Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; HbA_1c, hemoglobin A_1c; RR, relative risk.

Table S1 Multivariate analysis of the joint phenotype of low eGFR and history of cataract with plasma pentosidine levels analyzed as a continuous variable

	Group 1c	Group 2c	Group 4c
Low eGFR	No	Yes	Yes
History of cataract	Yes	Yes	No
	RR (95% CI)	RR (95% CI)	RR (95% CI)
Model 1 (without age in the model) a
Pentosidine	0.999 (0.998–1.002)	1.002 (1.001–1.004)	0.999 (0.998–1.001)
HbA1c (%)	1.52 (0.93–2.48)	0.70 (0.38–1.29)	1.26 (0.75–2.12)
Hypertension	1.32 (0.44–3.96)	9.04 (1.60–50.93)	12.39 (1.43–107.41)
Diabetic retinopathy	1.78 (0.48–6.64)	6.89 (1.82–26.04)	3.59 (0.95–13.55)
Model 2 (with age in the model) b
Pentosidine	0.999 (0.998–1.001)	1.002 (1.0002–1.003)	0.999 (0.998–1.001)
Age	1.12 (1.06–1.20)	1.25 (1.15–1.36)	1.09 (1.02–1.16)
HbA1c (%)	1.80 (1.05–3.10)	0.80 (0.39–1.63)	1.42 (0.81–2.49)
Hypertension	0.99 (0.31–3.20)	5.02 (0.79–31.94)	10.56 (1.19–93.61)
Diabetic retinopathy	2.09 (0.50–8.71)	8.25 (1.78–38.17)	4.13 (0.98–17.50)

Notes:

a Apart from pentosidine, only covariates (HbA_1c, history of hypertension and diabetic retinopathy) which were statistically significant in the final model are shown;

b apart from pentosidine, only covariates (HbA_1c, history of hypertension [P = 0.058], diabetic retinopathy) which were statistically significant in the final model are shown;

c group 3 is the referent category.

Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; HbA_1c, hemoglobin A_1c; RR, relative risk.

Table S2. Multivariate analysis of the joint phenotype of low estimated glomerular filtration rate and history of cataract surgery with plasma pentosidine levels as a binary variable

	Group 1c	Group 2c	Group 4c
Low eGFR	No	Yes	Yes
History of cataract surgery	Yes	Yes	No
	RR (95% CI)	RR (95% CI)	RR (95% CI)
Model 1 (without age in the model)a
Pentosidine	0.89 (0.30–2.62)	3.48 (1.24–9.76)	1.59 (0.76–3.32)
Hypertension	0.44 (0.13–1.49)	3.39 (0.63–18.40)	13.57 (1.64–111.93)
Diabetic retinopathy	2.84 (0.77–10.52)	6.45 (1.96–21.16)	3.21 (1.15–8.97)
Model 2 (with age in the model)b
Pentosidine	0.76 (0.25–2.33)	2.81 (0.91–8.71)	1.33 (0.61–2.89)
Age	1.14 (1.06–1.24)	1.21 (1.12–1.31)	1.08 (1.03–1.14)
Hypertension	0.26 (0.07–0.996)	1.29 (0.21–8.06)	9.97 (1.19–83.58)
Diabetic retinopathy	3.80 (0.95–15.17)	8.81 (2.33–33.35)	3.60 (1.20–10.74)

Notes:

a Apart from pentosidine, only covariates (history of hypertension and diabetic retinopathy) which were statistically significant in the final model are shown;

b apart from pentosidine, only covariates (history of hypertension and diabetic retinopathy) which were statistically significant in the final model are shown;

c group 3 is the referent category.

Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; RR, relative risk.

Table S3. Multivariate analysis of the joint phenotype of low estimated glomerular filtration rate and history of cataract surgery with plasma pentosidine levels analyzed as a continuous variable

	Group 1c	Group 2c	Group 4c
Low eGFR	No	Yes	Yes
History of cataract surgery	Yes	Yes	No
	RR (95% CI)	RR (95% CI)	RR (95% CI)
Model 1 (without age in the model)a
Pentosidine	1.001 (0.998–1.002)	1.002 (1.001–1.004)	1.001 (0.999–1.002)
Hypertension	0.47 (0.14–1.58)	3.25 (0.58–18.15)	13.42 (1.63–110.77)
Diabetic retinopathy	2.95 (0.80–10.93)	7.10 (2.13–23.69)	3.26 (1.17–9.12)
Model 2 (with age in the model)b
Pentosidine	1.000 (0.998–1.002)	1.002 (1.001–1.004)	1.001 (0.999–1.002)
Age	1.14 (1.06–1.23)	1.21 (1.12–1.32)	1.08 (1.03–1.14)
Hypertension	0.28 (0.07–1.05)	1.38 (0.21–9.6)	9.94 (1.18–83.49)
Diabetic retinopathy	3.86 (0.96–15.47)	9.79 (2.53–37.84)	3.67 (1.23–10.98)

Notes:

a apart from pentosidine, only covariates (history of hypertension and diabetic retinopathy) which were statistically significant in the final model are shown;

b apart from pentosidine, only covariates (history of hypertension and diabetic retinopathy) which were statistically significant in the final model are shown;

c group 3 is the referent category.

Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; RR, relative risk.