Table 1.

Clinical studies demonstrating the diversity of associations between circulating traditional lipid profiles and diabetic retinopathy

Study	Diabetes type	Type of DR	n	Blood lipids evaluated	Results
Cross-sectional studies
Brown et al [12]	T1D+T2D	Exudative DR	31	TC, TG	Increased serum TG in participants with vs without DR
Sacks et al [23]	T1D+T2D	DR (PDR, moderate or severe DMO) or ETDRS scale ≥20	2535	TC, TG, LDL-C, HDL-C	Higher TG and lower HDL with vs without DR, but not once adjusted for hypertension and HbA1c
Raman et al [22] (SN-DREAMS)	T2D	CSMO, non-CSMO	1414	TC, TG, HDL-C, LDL-C	High serum LDL-C, non-HDL-C and HDL-C ratio related to non-CSMO High serum TC related to CSMO
Benarous et al [11]	T1D+T2D	NPDR (mild, moderate, severe), PDR, DMO (mild, moderate, CSMO)	500	TC, TG, LDL-C, HDL-C, non-HDL-C	Serum lipids independently associated with CSMO only No associations with DR, mild or moderate DMO, or macular thickness
Wong et al [26] (MESA)	T1D+T2D	DR, DMO, CSMO STDR	778	TC, TG, LDL-C, HDL-C	No associations with any DR, DMO or CSMO
Cetin et al [13]	Not specified	NPDR, PDR, DME	199	TC, HDL-C, LDL-C, VLDL-C, TG	Serum lipid levels not associated with severity of DR or DMO
Tan et al [25] (SEED study)	T2D	DR, severe non-PDR, STDR, DMO, CSMO,	2877	TC, LDL-C	Higher TC and LDL-C associated with lower risk of any type of DR
Guerci et al [16]	T1D	DR, NPDR, PDR	341	Lp(a)	Higher Lp(a) levels were associated with more severe DR, and Lp(a) >300 mg/l (30 mg/dl) was associated with higher PDR
Longitudinal studies
Dodson and Gibson [15] (7 years)	T2D Hypertension	DR with exudative maculopathy	52	TC, HDL-C, HDL2, LDL-C, VLDL-C, TG	Higher HDL2 subfraction with exudative maculopathy
Klein etal [18] (WESDR; 30 years)	T1D	PDR, DMO	903	TC, HDL-C	Serum lipids not associated with incidence of PDR or macular oedema, nor was statin use
Chew et al [14] (ETDRS; 5 years)	T2D+T1D	Hard exudates	2709	TC, TG, HDL-C, LDL-C, VLDL-C	High TC, TG and LDL-C associated with higher risk of hard exudates
Miljanovic et al [20] (DCCT; 6.5 years)	T1D	CSMO, hard exudate, DR progression, PDR	1441	TC, LDL-C, HDL-C, TG, TC / HDL	Higher serum lipids associated with higher risk of CSMO and retinal hard exudates No lipids associated with DR progression or development of PDR after adjustment for HbA1c
Klein et al [17] (WESDR substudy; 5 years)	T1D	DR severity, PDR, hard exudate incidence and progression, DMO	251	TC/HDL	Univariate analyses: TC/HDL-C was associated with all incident retinal lesions Multivariate analyses: no association was significant
Morton et al [21] (ADVANCE trial 5 years)	T2D	New or worsening DR	11,400	Baseline HDL-C	HDL-C levels not related to DR
Lloyd et al [19] (EDC; 2 years)	T1D	DR (Airlie House Classification) Progression, PDR	657	TC, TG, LDL-C, HDL-C	TG and LDL-C predictive DR progression and of development of PDR
Singh et al [24] (DiaGene; 6.97 years)	T2D	NPDR, PDR	1886	Plasma Lp(a) levels Two SNPs modulating Lp(a) levels	No association between Lp(a) levels or SNPs with incident or prevalent DR
Meta-analyses
Yau et al [27] (META-EYE)	T1D+T2D	DR, PDR, STDR, DMO, CSMO	22,896	TC	Higher TC associated with higher prevalence of DMO
Zhou et al [28]	T1D+T2D	DR	4366	TC, TG, LDL-C, HDL-C	TC, TG,HDL-C: no difference betweenDR vs no DR LDL-C: higher in DR vs no DR

CSMO, clinically significant macular oedema; DR, diabetic retinopathy; EDC (Pittsburgh) Epidemiology of Diabetes Complications; HDL-C, HDL-cholesterol; LDL-C, LDL-cholesterol; Lp(a), lipoprotein(a); MESA, Multi-ethnic Study of Atherosclerosis; META-EYE, Meta-Analysis for Eye Disease; NPDR, non-proliferative diabetic retinopathy; SEED, Singapore Epidemiology of Eye Diseases; SN-DREAMS, Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study; T1D, type 1 diabetes; T2D, type 2 diabetes; TC, total cholesterol; WESDR, Wisconsin Epidemiologic Study of Diabetic Retinopathy