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. 2023 Feb 22;2023(2):CD013775. doi: 10.1002/14651858.CD013775.pub2

Summary of findings 2. Prognostic factors for the development and progression of PDR in people with diabetic retinopathy: systemic factors.

Population: people with diabetes 
Outcome: progression to PDR 
 
Prognostic factors
Study results: effect estimates (95% confidence interval (CI)) Certainty of evidence Plain text summary
HbA1c
(Refer to Table 9 for adjustment factors)
T1Dand T2D (follow‐up 2 to 24 years)
Adjusted OR ranged from 1.11 (0.93 to 1.32) to 2.10 (1.64 to 2.69)
Data from 77,075 participants in 7 studies 
Adjusted RR ranged from 1.30 (1.04 to 1.61) to 5.75 (1.54 to 21.4)
Data from 5,574 participants in 4 studies
Adjusted HR ranged from 1.09 (0.97 to 1.22; P = 0.164) to 1.43 (1.23 to 1.67)
Data from 8,219 participants in 4 studies  
Moderatea Increased HbA1c is likely to be associated with progression to PDR
Fasting plasma glucose
(Refer to Table 10 for adjustment factors)
T1Dand T2D (follow‐up 6 to 13 years)
Adjusted OR 1.38 (95% CI not reported)
Data from 4483 participants in 1 study
Adjusted HR 0.93§ (0.82 to 1.06)
Data from 2623 participants in 1 study
Adjusted standardised regression estimate 0.007 (SE 0.002).
Data from 927 participants in 1 study
Very lowa,b,c Evidence is very uncertain about the effect of fasting plasma glucose on risk of developing PDR
Diastolic blood pressure
(Refer to Table 11 for adjustment factors)
T1Dand T2D (follow‐up 4 to 25 years)
Adjusted OR ranged from 1.02 (0.93 to 1.05) to 2.50 (1.04 to 6.00)
Data from 6777 participants in 4 studies.
Adjusted HR ranged from 1.03 (1.00 to 1.05) to 1.15 (1.01 to 1.31)
Adjusted meta‐analysis HR 1.07 (0.96 to 1.18; Tau2 =0.00)
Data from 2724 participants in 2 studies
Very lowa,b,c Evidence suggesting that DBP is associated with progression to PDR is very uncertain (DBP was not an independent predictor for development of PDR when correcting for other important risk factors, including HbA1C and DR severity at baseline)
Systolic blood pressure
(Refer to Table 12 for adjustment factors)
T1Dand T2D (follow‐up 4 to 25 years)
Adjusted OR ranged from 0.91 (0.69 to 1.20) to 1.05 (95% CI not reported)
Data from 6777 participants in 4 studies
Adjusted RR 1.41 (1.17 to 1.70)Ϯ
Data from 3482 participants in 1 study
Adjusted HR ranged from 1.11 (0.98 to 1.25) to 1.14 (1.04 to 1.25)§§
Very lowa,b,c
 
Evidence suggesting that SBP is associated with progression to PDR is very uncertain (SBP was not an independent predictor for the development of PDR when correcting for other important risk factors, including HbA1C and DR severity at baseline)
Mean arterial pressure  T1D (follow‐up 6 years)
Adjusted OR (adjusted for HbA1c, age, sex, socioeconomic status, BMI, central retinal arterial equivalent, ocular perfusion pressure) 1.35 (0.91 to 2.00)
Data from 725 participants in 1 study
Very lowa,b,c
 
Evidence is very uncertain about the effect of mean arterial pressure on risk of developing PDR 
 
Dyslipidemia
(Refer to Table 13 for adjustment factors)
T1Dand T2D (follow‐up 5 years)
Adjusted HR ranged from 0.83 (0.47 to 1.47) to 0.86 (0.71 to 1.03)
Data from 58,070 participants in 2 studies
Lowa,b
 
Evidence suggests dyslipidaemia may not be associated with progression to PDR
Total cholesterol
(Refer to Table 14 for adjustment factors)
T1Dand T2D (follow‐up 4 to 12 years)
Adjusted OR 1.03 (95% CI not reported)
Data from 4483 participants in 1 study
Adjusted RR 1.8 (1.20 to 2.70)*
Data from 953 participants in 1 study
Adjusted HR 0.93 (0.81 to 1.07).
Data from 2623 participants in 1 study
Very lowa,b,c
 
Evidence suggesting that total cholesterol is associated with progression to PDR is very uncertain (total cholesterol was not an independent predictor for development of PDR when correcting for other important risk factors, including HbA1C and DR severity at baseline)
Triglycerides
(Refer to Table 15 for adjustment factors)
T1Dand T2D (follow‐up 7 to 24 years)
Adjusted RR (T1D) 1.55 (1.06 to 1.95)
Data from 368 participants in 1 study
Adjusted HR (T2D) 1.01 (0.91 to 1.12)
Data from 2623 participants in 1 study
Lowa,b Evidence suggests triglycerides may be associated with progression to PDR in T1D
LDL
(Refer to Table 16 for adjustment factors)
T1Dand T2D (follow‐up 6 to 7 years)
Adjusted HR (T2D) 0.89 (0.78 to 1.03)
Data from 2623 participants in 1 study
Very lowa,b,c
 
Evidence is very uncertain about the effect of LDL on risk of developing PDR
HDL
(Refer to Table 17 for adjustment factors)
T1Dand T2D (follow‐up 6 to 7 years)
Adjusted HR (T2D) 0.88 (0.76 to 1.01)
Data from 2623 participants in 1 study
Very lowa,b,c
 
Evidence is very uncertain about the effect of HDL on risk of developing PDR
Nephropathy (biomarker of renal function)
(Refer to Table 18 for adjustment factors)
T1Dand T2D (follow‐up 5 to 8 years)
Adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42)
Data from 76,300 participants in 2 studies
Adjusted HR ranged from 1.29 (0.99 to 1.67) to 9.7 (8.15 to 11.5)
Data from 58,070 participants in 2 studies
Very lowa,b,c
 
Evidence is very uncertain about the effect of nephropathy on risk of developing PDR
Proteinuria (biomarker of renal function)
(Refer to Table 19 for adjustment factors)
T1Dand T2D (follow‐up 4 to 25 years)
Adjusted OR ranged from 0.90 (0.25 to 3.32) to 5.17 (0.49 to 54.3)
Data from 3664 participants in 3 studies
Adjusted RR 2.50 (1.1 to 5.8)
Data from 953 participants in 1 study
Very lowa,b,c
 
Evidence is very uncertain about the effect of proteinuria on risk of developing PDR
Albumin excretion rate (biomarker of renal function)
(Refer to Table 20 for adjustment factors)
T1Dand T2D (follow‐up 5 to 7 years)
Adjusted OR (T1D) 2.40 (1.09 to 5.29)
Data from 725 participants in 1 study
Adjusted RR (T2D) 1.34 (0.31 to 5.82)
Data from 56 participants in 1 study
Lowa,b Evidence suggests albumin excretion rate may be associated with progression to PDR in T1D
Albumin creatinine ratio (biomarker of renal function)
(Refer to Table 21 for adjustment factors)
T2D (follow‐up 6 to 8 years)
Adjusted HR ranged from 1.22 (1.20 to 1.78) to 6.65 (3.92 to 11.29)
Data from 2327 participants in 2 studies
Moderatea Evidence suggests albumin creatinine ratio is likely associated with increased risk of progression to PDR in T2D 
Estimated glomular filtration rate (biomarker of renal function)
(Refer to Table 22 for adjustment factors)
T2D (follow‐up 4 to 8 years)
Adjusted HR ranged from 2.55 (1.22 to 5.35) to 4.22 (1.27 to 14.07)
Data from 2501 participants in 2 studies
Moderatea Evidence suggests estimated glomerular filtration rate is likely associated with progression to PDR in T2D 
Creatinine (Refer to Table 23 for adjustment factors) T2D (follow‐up 4 to 8 years)
Adjusted RR 4.8 (95% CI not reported)
Data from 953 participants in 1 study
Adjusted HR ranged from 1.11 (0.99 to 1.23) to 2.37 (1.70 to 3.29)
Data from 4719 participants in 2 studies
Adjusted meta‐analysis HR 1.61 (0.77 to 3.36; Tau2 = 0.28)
Data from 4660 participants in 2 studies
Very lowa,b,c
 
The evidence is very uncertain about the effect of creatinine on risk of developing PDR

BMI: body mass index; CI: confidence interval; HDL: high‐density lipoprotetin; HR: hazard ratio; LDL: low‐density lipoprotein;OR: odds ratio; PDR: proliferative diabetic retinopathy; RR: risk ratio; T1D: type 1 diabetes; T2D: type 2 diabetes

aDowngraded by one level for risk of bias: more than 80% of studies at high or unclear risk of bias
bDowngraded by one level for inconsistency: significant differences in effect estimates reported by studies 
cDowngraded by one level for imprecision: wide 95% CIs

§Study did not adjust for duration of DM or DR severity at baseline (Roy 2006)
ϮStudy did not adjust for DR severity at baseline (Janghorbani 2000)
§§Study did not adjust for duration of DM or DR severity at baseline (WESDR (Report XXII))
*Study did not adjust for HbA1c or DR severity at baseline (Nelson 1989)