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1 w wz 16«1y Kor. J. Clin. Pharm., Vol. 16, x y x B»C s w s w w Pattern and Management of Dyslipidemia in Type 2 Diabetes Patients in Korea Kyong Ju Jeong a and Seung Ki Cho b a Dept of Pharmacy, Pundang CHA General Hospital b Department of Pharmacology, College of Medicine, Pochon CHA University, Sungnam, Kyonggi-do, , Korea Dyslipidemia is an important CHD risk factor in diabetic patients. We conducted this study to assess the pattern of dyslipidemia in type 2 diabetes patients, to examine the demographic and clinical factors associated with dyslipidemia and to evaluate attaining within the lipid target goals and treatment strategies. A retrospective analysis was conducted among patients diagnosed type 2 diabetes at outpatient clinic in endocrinology between January 2003 and December Clinical history and physical examination were reviewed and laboratory data including blood glucose, HbA1c, lipid levels were recorded sequentially at least 1 year. In 882 patients with type 2 diabetes, 437 patients (49.6%) have dyslipidemia and 73% of them (319 patients) received lipid-lowering agents. 244 patients (94 males, 150 females, mean age 60 years old) were susceptible to analyses. The most frequent pattern of dyslipidemia is high LDL level and high TG levels (28%). Metabolic syndrome and macrovascular complication were significant negative independent association with lipid levels within the target goals (p<0.05). Only 15.2% (19 males, 18 females) attained within the lipid target goals. Patients with diabetic dyslipidemia need maximization of lipid-lowering agent, increasing the fibric acid derivatives prescription and the effort to correction of low HDL and/or high TG. Key words Dyslipidemia, Type 2 diabetes, Pattern of dyslipidemia, Lipid target goal w w y yƒ w ƒ y y š y jš w x y w ƒƒ 3 4 wš p w ù 10 2 ƒ. x y 1) w ƒ j š2,3) y 50-80% y ƒ x» š x š. 2x y y 4-6) wù, x y š, total cholesterol( w TC) LDL-cholesterol( w LDL-C) ƒ û HDLcholesterol( w HDL-C) triglyceride( w TG) ƒ Correspondence to :» s w w» û k 351 Tel: , Fax: ddoldolikr@yahoo.co.kr y ƒ k. 2x y 4-7) x s w x y x ü š 4-6), 2x š v e ge w TGƒ ûš HDL-C û w LDL-C HDL-Cƒ š š š. 8,9) m w 2x y ùkü y p w š y x s w š w. w y x p t x (lipid target goal) sƒw y ww e z w š w ¾ ü ü y 2x y 46

2 2x y x » zw w, n», w, šx y, d, x e(, š x,» ) 1 w. 882 y 437 x e 1z x ùkü š( y 49.6%, s³ 59.8, 60.9% ) 319 ( y 73%) w n. w n 2x y 1z x x e z (follow-up)ƒ y 244 š y l wš m w. e t x x te xz w y» œ x mg/dl, HbA1c 7%, LDL- C 100 mg/dl, HDL-C û 45 mg/dl, 55 mg/dl, TG 150 mg/dl w. 10) œ y w z (Metabolic syndrome)» NCEP ATPIII(US National Cholesterol Education Program: Adult Treatment Panel III) (x ƒ û 35 e, 31 e ), TGƒ 150 mg/dl, HDL-C û 40 mg/dl, 50 mg/dl, x» 130 mmhg» 85 mmhg, œ x 110 mg/dl e 5 w 3 w z w. x w» (neuropathy), (nephropathy), (retinopathy) ù w š w. x w» y(coronary artery disease), x y(cerebrovascular disease), y (peripheral arterial disease) ù» y š w š w. šx» x w w šx w. SPSS 12.0K l w, 95% w š, x te y p» w p z (logistic regression analysis) w. y p w n 2x y 1z x x e z ƒ w ƒ w y 244 š û 94, 150. s³ 60, s³ (body mass index, w BMI) 25.2kg/m 2, s³» 10.4, s³ HbA1c 8.32% x ƒ š. w y 70.9% z ƒ š š, x w 27.5%, x w 52.9% ƒ š (Table 1). ƒ x w sulfonylurea biguanide ƒƒ 31% wš. x s w x x x LDL-C TGƒ xkƒ 28% ƒ w š, LDL-C xk 19% ùkü ƒ w statin 77% y. y» x x 70% LDL-Cƒ t ùkü š, û 30%, 51% HDL-Cƒ t, 74% y TGƒ t e ùkü. x e z cholesterol e» e ùkû (paired t-test, p ). Table 1. Demographics and clinical characteristics All (n=244) Male (n=94) Female (n=150) Age, years a Duration of diabetes, years a BMI, kg/m 2 a HbA1c, % a Metabolic syndrome, % b Macrovascular complication, % b Microvascular complication, % b (*= p ) a Values are mean(ûsd) b Values are percentages(95% CI) 60.2(±11.3) 10.4(±5.8) 25.2(±6.8) 8.3(±1.4) 70.9( ) 27.5( ) 52.9( ) 56.7(±11.6)* 9.47(±5.3)* 24.8(±2.5) 8.2(±1.5) 66.6( ) 24.5( ) 42.6( ) 62.5(±10.6)* 11.0(±6.1)* 25.6(±8.5) 8.4(±1.4) 73.3( ) 29.3( ) 59.3( )

3 48 Kor. J. Clin. Pharm., Vol. 16,. 1, 2006 x y,,», BMI, z, HbA1c, šx w ƒ x x» n z w.» r, HbA1cƒ LDL-Cƒ y ƒ š, BMIƒ 25 w y TG HDL-Cƒ t e ù. z y y w LDL-C, TG, HDL-C ƒ w. û HDL-C» e w y ƒ w (Table 2). n z(follow-up) x e» w ù, z 2x y TG, HDL-C, HDL-C wy, šx y HDL-C wy ƒ w (Table 3). tx y xz «š» x t LDL, HDL-C, TG ƒ w y %(û 20.2%, 12%) w.» w wƒ ƒ te w w y 26.6 % ƒ y ƒ te ù w HDL-C. w te w w y 42.6% ƒ y ƒ te ù w TG HDL-C. w ƒ w te w w y 15.6%(û 8.5%, 20%) ùkû (Fig. 1, Table 4). e w e û w ù ùkû (p= 0.023)(Fig 2, Table 4). œ y w x w w y 176 (72%) š, Table 2. Prevalence of dyslipidemia in initial lab data according to selected demographic and clinical variables. Values are percentage of patients Gender Male Female Age, years < Duration of DM, years > 10 HbA1c, % < > 8 BMI 25 > 25 Metabolic syndrome Hypertension a Fisher s exact test b Chi-square test Patients, n LDL initial ( 130 mg/dl) TG initial ( 150 mg/dl) HDL initial ( 45 mg/dl men, 55 mg/dl women)

4 2x y x 49 Table 3. Prevalence of dyslipidemia in follow up lab data according to selected demographic and clinical variables. Values are percentage of patients Gender Male Female Age, years < Duration of DM, years > 10 HbA1c, % < > 8 BMI 25 > 25 Metabolic syndrome Hypertension a Fisher s exact test b Chi-square test Patients, n LDL cholesterol ( 130 mg/dl) TG ( 150 mg/dl) HDL cholesterol ( 45mg/dl men, 55mg/dl women) Fig 2. Sex disparity in the outside of lipid target goals. Fig 1. Percentage of patients with none, one, two, three lipid values outside of the recommended clinical target. z ƒ š y 173 (70.9%), x w y ƒ š y 37 (15%), x y ƒ š y 33 (13.5%). x w ƒ š y 109 (44.7%), 33 (13.5%), (13.9%).

5 50 Kor. J. Clin. Pharm., Vol. 16,. 1, 2006 Table 4. Percentages of patients (total = 244) with none, one, two, three lipid values outside of the recommended clinical target established by the American Diabetes Association Patients (n=244) n (%) n out of target 37 (15.2) One out of target LDL TG HDL Two out of target LDL + TG LDL + HDL TG + HDL Three out of target 65 (26.6) 20 (8.2) 12 (4.9) 33 (13.5) 104 (42.6) 33 (13.5) 27 (11.1) 44 (18.0) 38 (15.6) tx n z t x w, BMI,»w, HbA1c, z, x w, x w w pz (logistic regression analysis) w., z x w t x w w ùkû (p=0.05). š Male (n=94) n (%) 19 (20.2) 28 (29.8) 10 (10.6) 8 (8.5) 10 (10.6) 39 (41.5) 16 (17.0) 8 (8.5) 15 (16.0) 8 (8.5) Female (n=150) n (%) 18 (12.0) 37 (24.7) 10 (6.7) 4 (2.7) 23 (15.3) 65 (43.3) 17 (11.3) 19 (12.7) 29 (19.3) 30 (20.0) y s³ HbA1c 8.32% š w x. wz «š 7% û x w e ƒ v w. wz «š HbA1c 1% û w x (relative risk) 15-30% w š šwš. 10) x ù. 4,6,11) y k w x ƒ. y ƒ û w w ù ƒ š» ¼» x t x û w û š (p=0.023). û w š e û w. k y û y w x w n w ùkü š š wš. 71%ƒ z ƒ š 12) š, w, x e ƒ, x 13) z» y x w ƒ š. 14) x e ƒ xz «š 10) National Cholesterol Education 15) Program(NCEP) Adult Treatment Panel III guideline» wš. ww e «š w txx(metabolic phenotype), z ƒ š x sw w w y y wì ww w. w 16) 70% y LDL-C ƒ š y LDL-C y w š w y w ùkü šƒ š, 80% 17) w y ƒ x š(major vascular event)ƒ w ù w w šƒ. 17,18) 2x y e ƒ t x x w. šx e,, aspirin n, š w n sw. ù w n 19) t x r y 15.2%(û 20.2%, 12%) k 4) ƒ û. û t x w e w š w w š. w ƒ HMG-CoA reductase inhibitor( w statins) 77% y n š ù n z eš. ƒ ³ 20) LDL-C w w statins n ƒw x ƒ w ¾ n w v ƒ. w x 22% š 17) fibrates. Fibrates y š x z HDL-C ƒ j z. Fibrate n w TG 16,21) 50% ¾ š HDL-C 10% ü ƒ ùkü. 22,23) Fibrates HDL, LDL-Cƒ û y statins z šƒ 24) LDL-Cƒ 100 mg/dl HDL-Cƒ û statins gemfibrozil n w š w. 17) w ƒ wš n - w ƒ v w. w y w ƒ 2x y x tw š w»» y ³ ƒ v w š. y e ƒ wš y t e w»¾ ƒ v w y y

6 2x y x 51 e w w œ w š. š x 1. Korea national statistical office. The number of major cause of deaths potal_01/potal_0106/index. jsp. 2. Roper NA, Bilous RW, Kelly WF, et al. Excess mortality in a population with diabetes and the impact of material deprivation: longitudinal, population based study. BMJ 2001; 322: Pyorala K, Pedersen TR, Kjeksus J, et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastin Survival Study(4S). Diabetes Care 1997; 20: Al-Adsani A, Memon A, Surech A. Pattern and determinants dyslipidaemia in type 2 diabetes mellitus patients in Kuwait. Acta Diaetol 2004; 41: Cook CB, El-Kebbi IM, Erdman DM, et al. The Pattern of dyslipidemia among urban African-Americans with type 2 diabetes. Diabetes Care 2000; 23: Ismail IS, Nazaimoon W, Mohamad R et al. Ethnicity and glycemic control are major determinants of diabetic dyslipidemia in Malaysia. Diabetes UK. Diabetic Medicine 2001; 18: Turner RC, Millns H, Neil HAW et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23) BMJ 1998; 316: Cowie CC, Howard BV and Harries MI. Serum lipoproteins in African-Americans and whites with non-insulin dependent diabetes in the US population. Circulation 1994; 90: Summerson JH, Konen JC and Dignan MB. Racial differences in lipid and lipoprotein levels in diabetes. Metabolism 1992; 41: American diabetes association. Standards of medical care for patients with diabetes mellitus. Diabetes care 2002; 25: Ko GT, Cockram CS, Critchley JA et al. Glycemic control and obesity are the major determinants of diabetic dyslipidemia in Hong Kong Chinese. Diabetes Metab 2001; 27: Nau DP and Mallya U. Sex Disparity in the management of dyslipidemia among with type 2 diabetes mellitus in a managed care organization. Am J Manag Care 2005; 11(2): Tchernof A, lamarche B, Prud Homme D et al. The dense LDL phenotype: association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes care 1996; 19: Austin MA, McKnight B, Edward KL et al. Cardiovascular disease mortality in familial forms of hypertriglyceridemia: a 20-year prospective study. Circulation 2000; 101: Talbert RL. Role of the National Cholesterol Education Program Adult Treatment Panel III guidelines in managing dyslipidemia. Am J Health-Syst Pharm 2003; 60: S Ayyobi AF and Brunzell JD. Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia. Am J cardiol 2003; 92: 27J-33J. 17. Vijan S and Hayward RA. Pharmacologic lipid-lowering therapy in type 2 Diabetes mellitus: Backgroud paper for the American college of physicians. Ann Intern Med 2004; 140: Meigs JB, Singer DE, Sullivan LM et al. Metabolic control and prevalent cardiovascular disease in non-insulindependent diabetes mellitus (NIDDM): The NIDDM Patients Outcome Research Team. Am J Med 1997; 102: Snow V, Weiss KB, and Mottur-Pilson C. The evidence base for tight blood pressure control in the management of type 2 diabetes mellitus. Ann Intern Med 2003; 138: Scheeman G and Hiatt J. Dose response characteristics of cholesterol-lowering drug therapies: implications for treatment. Ann Intern Med 1996; 125: Best JD and O Neal DN. Diabetic dyslipidemia current treatment recommendations. Drugs 2000; 59(5): Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 1998; 21(1): Lahdenpera S, Tilly-Kiesi M, Vurien-Markkola H et al. Effect of gemfibrozil on low-density lipoprotein particle size, density distribution and composition in patients with type 2 diabetes. Diabetes Care 1993; 16: Rubins HB, Robins SJ, Collins D et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study group. N Engl J med 1999; 1:

16(1)-3(국문)(p.40-45).fm

16(1)-3(국문)(p.40-45).fm w wz 16«1y Kor. J. Clin. Pharm., Vol. 16, No. 1. 2006 x w$btf3fqpsu'psn û w m w Department of Statistics, Chonnam National University Eunsik Park College of Natural Sciences, Chonnam National University