Pathophysiology/Complications N A L
A R T I C L E
High Serum Lipoprotein(a) Levels in Korean Type 2 Diabetic Patients With Proliferative Diabetic Retinopathy CHUL-HEE KIM, MD HYUNG-JOO PARK, MD JOONG-YEOL PARK, MD
SUNG-KWAN HONG, MD YOUNG-HEE YOON, MD KI-UP LEE, MD
OBJECTIVE — To examine the possible association between serum lipoprotein(a) [Lp(a)] concentration and proliferative diabetic retinopathy (PDR) in Korean patients with type 2 diabetes.
leading to PDR. However, only a few studies have dealt with this matter, with controversial results (8-11). This study was undertaken to find out whether high serum Lp(a) levels are found in type 2 diabetic patients with PDR.
RESEARCH DESIGN AND
METHODS— This study was performed in 412 type 2 diabetic patients RESEARCH DESIGN AND METHODS— A total of 412 Korean outpatients with type attending a university hospital (the Asan 2 diabetes were examined. Diabetic retinopathy was determined by an ophthalmologist using Medical Center) in Seoul, Korea. The diagfundoscopic examination. Serum Lp(a) levels were measured by two-site sandwich enzyme- nosis of type 2 diabetes was based on clinlinked immunosorbent assay. ical characteristics that included 1) no episodes of ketoacidosis; 2) diagnosis of RESULTS — The patients with PDR had higher serum Lp(a) levels than those with no dia- diabetes after 30 years of age; and 3) treatbetic retinopathy or with nonproliferative diabetic retinopathy (NPDR). Multiple logistic ment by diet or oral hypoglycemic agents regression analysis showed that high serum Lp(a) levels and the presence of diabetic nephropa- or fasting serum C-peptide values >0.30 thy were independent variables having a statistically significant association with PDR. nmol/1 in patients using insulin. Of the CONCLUSIONS — Korean type 2 diabetic patients with PDR had higher serum Lp(a) lev- subjects, 25% were using insulin and 61% els versus those with no diabetic retinopathy or with NPDR. Although these results suggest that were using oral hypoglycemic agents. Arterial blood pressure was measured Lp(a) might play a role in the occlusion of retinal capillaries leading to PDR, further prospecwith a mercury sphygmomanometer in the tive studies are required to prove the causal relationship. sitting position after a 10-min rest. Serum Diabetes Care 21:2149-2151, 1998 glucose, triglycerides, and total cholesterol levels were measured using an autoanalyzer with enzymatic techniques. HDL cholesroliferative diabetic retinopathy (PDR) covalently linked to apo B-100 by disulfide terol was measured after heparin and manis the most common cause of acquired bridges (6). Because of the structural simi- ganese chloride precipitation. HbAi was blindness in adults. Although a recent larity of apo(a) to plasminogen, Lp(a) has measured by affinity chromatography study by the Diabetes Control and Com- been suggested to have antifibrinolytic (Isolab, Akron, OH) (normal range 4-8%). plications Trial (DCCT) Research Group properties (7). High serum Lp(a) levels have Serum C-peptide was measured by radioim(1) clearly demonstrated that intensified thus been shown to be an independent risk munoassay (Daiichi, Tokyo). Patients colinsulin therapy could effectively delay the factor for atherogenesis and thromboem- lected timed overnight urine samples for the onset and progression of retinopathy in bolic events in both diabetic and nondia- determination of albumin excretion rate (AER) by radioimmunoassay (Diagnostic type 1 diabetes, studies performed in type betic subjects. Los Angeles, CA). MicroalbuminProducts, 2 diabetes have suggested that multiple Capillary occlusion is a frequent finduria was defined as AER 20-200 ug/min factors along with glycemic control deter- ing in diabetic retinopathy and is believed and overt proteinuria as AER >200 ug/min mine the risk of PDR (2-5). to play an important role in the developLipoprotein(a) [Lp(a)] is a plasma com- ment of PDR. High serum Lp(a) might play in at least two of the three measurements. plex composed of apolipoprotein(a) [apo(a)] a role in the occlusion of retinal capillaries Serum Lp(a) levels were measured by onestep sandwich enzyme-linked immunosorbent assay using monoclonal antibodies (Immuno, Vienna). From the Departments of Internal Medicine (C.-H.K., H.-J.P, J.-Y.E, S.-K.H., K.-U.L.) and Ophthalmology Fundoscopic examination was per(Y.-H.Y.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. formed by a retinal specialist (Y.-H.Y.) Address correspondence and reprint requests to Ki-Up Lee, MD, Department of Internal Medicine, Asan using ophthalmoscope and/or biomicroMedical Center, Song-Pa PO. Box 145, Seoul 138-600, Korea. E-mail:
[email protected]. Received for publication 29 May 1998 and accepted in revised form 19 August 1998. scope through dilated pupils. The findAbbreviations: AER, albumin excretion rate; apo(a), apolipoprotein(a); DCCT, Diabetes Control and ings were graded as 1) no signs of diabetic Complications Trial; Lp(a), lipoprotein(a); NPDR, nonproliferative diabetic retinopathy; OR, odds ratio; PDR, retinopathy, 2) nonproliferative diabetic proliferative diabetic retinopathy. retinopathy (NPDR), and 3) PDR. IndividA table elsewhere in this issue shows conventional and Systeme International (SI) units and conversion factors for many substances. uals were classified as having PDR if they
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DIABETES CARE, VOLUME 21, NUMBER 12, DECEMBER
1998
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Lp(a) and proliferative
diabetic
retinopathy
Table 1—Clinical and laboratory characteristics of the subjects according to retinopathy groups
n Age (years) Diabetes duration (years) BM1 (kg/m2) Fasting serum glucose (mmol/1) HbA! (%) C-peptide (nmol/1) Blood pressure (mmHg) Systolic Diastolic Cholesterol (mmol/1) Triglycerides (mmol/1) HDL cholesterol (mmol/1) AER (pg/min) Lp(a) (mg/dl)
No retinopathy
NPDR
PDR
218 55 ±0.7 5.6 ±0.3 24.8 ±0.2 9.7 ±0.2 11.4 + 0.3 0.8 ± 0.03
143 59 ± 0.8 11.6 ±0.4* 23.6 ±0.2 11.0 ±0.3* 12.3 ±0.3 0.7 ±0.03
51 58 ±1.5 13.8 ±0.9* 23.5 ±0.4 10.3 ±0.6 11.7 ±0.4 0.6 ±0.04
143 ± 1.4 85 ±0.7 5.7 ±0.07 2.7 ±0.12 1.1 ±0.02 23 ±3.0 (8, 1-237) 13.1 ± 1.1 (6.5, 1.0-75.9)
148 ±1.8 87 ±1.0 5.6 ±0.11 2.3 ±0.14 1.2 ±0.03 64 ± 8.4* (21,2-517) 19.3 ±1.5 (13.7, 1.0-80.3)
150 ±2.9 86 ±2.0 6.0 ±0.25 2.3 ±0.22 1.2 ±0.04 76 ±15.4* (29, 4-525) 32.2±3.3*t (27.8, 1.0-97.7)
Data are means ± SEM or means ± SEM (median, range). *P < 0.05 vs. no retinopathy; ?P < 0.05 vs. NPDR group.
had new vessels, vitreous hemorrhage, vitreoretinal traction, or retinal detachment believed to be attributable to diabetic neovascularization.
Statistical analysis Data are expressed as mean ± SEM or median (range). Variables that showed skewed distribution, such as serum triglyceride levels and AER, were log-transformed before analysis. Comparisons between groups were made by analysis of variance with Duncan's multiple range test or Kruskal-Wallis test where appropriate. Multiple logistic regression analysis was performed to find independent factors associated with the presence of PDR. A P value
