Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus

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Abstract. Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated ...
ACTA

Acta Diab 28:158-161, 1991

DIABETOLOGICA 9 Springer-Verlag 1991

Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus Giacomo Ruotolo, Adele Zoppo, Mariella Parlavecchia, Beatrice Giberti, and Piero Micossi Department of Medicine and Laboratory of Lipoprotein Metabolism, Scientific Institute San Raffaele, University of Milan, Via Olgettina 60, 1-20132 Milan, Italy

Abstract. Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated that apolipoprotein (a) [apo (a)] levels are positively associated with an increased risk of macrovascular disease, we investigated whether apo (a) levels are elevated in both types of diabetes mellitus and may thus represent an independent risk factor for atherosclerotic disease. Apo(a) concentrations in type 1 diabetic patients were not significantly different from matched controls (276+_78 vs 149_+46 units/l). Type 2 diabetic patients had considerably higher levels of apo(a) than matched controls (471 _+89 vs 221 _+61 units/l, P = 0.06), though the difference was not statistically significant. However, concentrations of apo(a) were above 300units/l in 36% of type I and 67% of type 2 diabetic patients, but in only 14% and 25% respectively of matched control subjects. Plasma triglycerides were positively and independently correlated with apo (a) levels in both diabetic and non-diabetic subjects. On the other hand, no significant correlation was found between apo (a) levels and glycosylated haemoglobin, total cholesterol or high density lipoprotein cholesterol in any of the groups studied. In conclusion, apo (a) levels are not significantly elevated either in type I or type 2 diabetic patients without proteinuria and in moderate metabolic control; however, levels above 300 units/1 were 2.6 times more frequent in both types of diabetes mellitus than in carefully age-, sex-, and weightmatched control subjects. Key words: Lipoprotein (a) - Triglycerides - Type 1 diabetes mellitus - Type 2 diabetes mellitus

Introduction Lipoprotein (a) [Lp (a)] was demonstrated in human plasma more than 25 years ago by Berg [1]. Its composition Offprint requests to." G. Ruotolo

is similar to that of low density lipoproteins (LDL), the only major differences being the presence of a characteristic apolipoprotein, apolipoprotein (a), [apo (a)], and the high polysaccharide content (30% by weight) [2]. Several reports have indicated that Lp (a) is positively associated with increased coronary heart disease (CHD) morbidity [3-10]. Patients with both type 1 and type 2 diabetes mellitus also have an increased incidence of CHD [11, 12], and lipid abnormalities may represent one of the factors predisposing diabetic subjects to accelerated atherosclerosis [13]. A preliminary study reported no significant differences in Lp(a) levels between diabetics (type 1 and type 2) and non-diabetics [14], while a recent study has suggested increased levels in type 1 diabetes mellitus [15]. Moreover, recent data demonstrate a positive correlation between Lp(a) and glycosylated haemoglobin in white diabetic children [16] and a significant effect of improved glycaemic control on Lp (a) levels in type 1 diabetics [17]. In this study, we further examine the relationships between the two types of diabetes mellitus and apo (a) levels, in order to understand if Lp (a) may play a role as an important risk factor in diabetes. In addition, we have examined possible associations of apo (a) with other metabolic parameters, such as plasma lipids and glycaemic control.

Subjects and methods The study population consisted of 26 diabetic patients, 14 males and 12 females, age range 19-78 years, with body mass index (BMI) 17.4-35.6, and glycosylated haemoglobin (HbAlc) values 5.913.6% (normal range 4-6%). Twelve patients had type 2 (8 male, 4 female) and 14 (6 male, 8 female) in type 1 diabetes mellitus. The duration of the disease ranged from I to 15 years; no patients had evidence of clinical nephropathy or albuminuria. In the type 2 diabetic group, 8 patients were on oral hypoglycaemic agents and 4 were receiving insulin. Twenty-six subjects with normal glucose tolerance, matched for sex, age and BMI, served as controls (Table I). Blood samples were collected by venipuncture after an overnight fast. Serum was separated by low-speed centrifugation and stored in aliquots at - 20 ~ until determination of total cholesterol, triglycerides, HDL cholesterol and apo (a) levels.

G. Ruotolo et al.: Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus

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Table 1. Study population characteristics 900 n (M/F)

Age (years)

BMI (kg/m 2)

Type 1 diabetics Controls

6/8 6/8

38.4+_3.7 20.7+_1.0 8.8• 39.5• 19.8+_0.4 5.0+_0.4

Type 2 diabetics Controls

8/4 8/4

66.1 • 65.8-+ 2.2

0 0

HbAI~ (%) D v ~. 6oo c (D

25.2+_1.9 9.9• 24.8 • 5.2 +_0.5

HDL cholesterol (mmol/1)

Type 1 diabetics Controls

4.66•

1.40__.0.20

1.14-1-0.05"* 276+_78

5.41 +_0.36

0.89+0.09

1.45_+0.05

Type2 diabetics Controls

5.39_+0.41 2.21+_0.52"* 0.88+_0.08** 471_+89 5.72+_0.28 1.07_0.15

1.35+-0.10

Apolipoprotein (a) (units/l)

o o

S

o

0

0

~_ 300 ......................... Q....................................... 9 .............

o

Q_

8

8