Upsala J Med Sci 87: I 1 1 - 1  17. 1982 

Fatty Acid Composition of Serum Lipids in Diabetic Children 
and their Matched Healthy Controls 
U .  Ewald', I.-B. GustafssonI, T. Tuverno' a n d  B. Vessby' 

Dapurtment of Purdiatric,s' utzd Grrirrtric..y', Uniivr.<ity Hospittrl, Uppsttltr , S\twietI 

ABSTRACT 

T h e  f a t t y  a c i d  c o m p o s i t i o n s  of t h e  s e r u m  c h o l e s t e r o l  esters, phospholipids a n d  
t r i g l y c e r i d e s  w e r e  d e t e r m i n e d  in 28 insulin-dependent d i a b e t i c  c h i l d r e n  a n d  1 3  h e a l t h y  

c o n t r o l s .  T h e  d i a b e t i c  c h i l d r e n  w e r e  o n  a r e g u l a t e d  d i e t  a n d  t h e  d i s e a s e  w a s  under g o o d  

c o n t r o l .  T h e  r e l a t i v e  c o n t e n t s  of l i n o l e i c  a n d  a r a c h i d o n i c  a c i d s  w e r e  h i g h e r  in t h e  s e r u m  

lipids of t h e  d i a b e t i c s  t h a n  in t h e  c o n t r o l s  as could be e x p e c t e d  f r o m  t h e  d i e t a r y  a d v i c e  
given. H o w e v e r ,  t h e  d e g r e e  of d i a b e t i c  c o n t r o l  w a s  n o t  s i g n i f i c a n t l y  c o r r e l a t e d  to t h e  
f a t t y  a c i d  c o n t e n t  of a n y  lipid f r a c t i o n .  T h e  s e r u m  c o n c e n t r a t i o n  of a p o l i p o p r o t e i n  f a p o )  
A-I w a s  d i r e c t l y  c o r r e l a t e d  to t h e  c o n t e n t  of p o l y u n s a t u r a t e d  fat a n d  t h e  r a t i o  b e t w e e n  
p o l y u n s a t u r a t e d  a n d  s a t u r a t e d  f a t t y  a c i d s  in t h e  t r i g l y c e r i d e s .  T h e  a p o  A-I1 c o n c e n t r a t i o n  

w a s  s i g n i f i c a n t l y  c o r r e l a t e d  t o  t h e  r a t i o  b e t w e e n  homo-gamma-linolenic a n d  a r a c h i d o n i c  

a c i d  in a l l  s e r u m  lipid e s t e r s .  No s i m i l a r  r e l a t i o n s h i p s  w e r e  s e e n  a m o n g  t h e  h e a l t h y  

c o n t r o l s .  T h e  d i f f e r e n t  r e l a t i o n s h i p s  b e t w e e n  s e r u m  a p o l i p o p r o t e i n  c o n c e n t r a t i o n s  a n d  t h e  

f a t t y  a c i d  c o m p o s i t i o n  in s e r u m  in d i a b e t i c s  a n d  c o n t r o l s  i s  c o m p a t i b l e  w i t h  t h e  

h y p o t h e s i s  t h a t  n o t  only t h e  q u a n t i t y  b u t  a l s o  t h e  q u a l i t y  of t h e  s e r u m  l i p o p r o t e i n s  a r e  

d i f f e r e n t  in t h e s e  t w o  c a t e g o r i e s  of c h i l d r e n .  

INTRODUCTION 

J u v e n i l e  o n s e t ,  insulin-dependent d i a b e t i c s  show a n  i n c r e a s e d  i n c i d e n c e  of e a r l y  

a t h e r o s c l e r o t i c  c a r d i o v a s c u l a r  d i s e a s e .  An i n c r e a s e d  a m o u n t  of p o l y u n s a t u r a t e d  f a t t y  

a c i d s  ( P U F A )  in t h e  d i e t  c o n t r i b u t e s  to a r e d u c t i o n  of a t h e r o s c l e r o t i c  c a r d i o v a s c u l a r  
d i s e a s e ,  at least in n o n d i a b e t i c s  (3, 14, 16). A r e c e n t  s t u d y  s u g g e s t s  t h a t  a n  i n c r e a s e d  
i n t a k e  of P U F A  d e c r e a s e s  t h e  i n c i d e n c e  of v a s c u l a r  c o m p l i c a t i o n s  i n  a d u l t  o n s e t  d i a b e t i c s  

(10). T h e  m e c h a n i s m  f o r  t h i s  b e n e f i c i a l  effect i s  n o t  c l e a r .  T h e  p o l y u n s a t u r a t e d  f a t t y  a c i d  

a r a c h i d o n i c  a c i d  (20:4) is t h e  p r e c u r s o r  of t h r o m b o x a n e  A 2  (TXA2) a n d  p r o s t a c y c l i n  
(PGIz), a n d  e i c o s a p e n t a e n o i c  a c i d  (20:5) i s  t h e  p r e c u r s o r  of t h e  c o r r e s p o n d i n g  T X A 3  a n d  
PGI3. In e s c i m o e s  a v e r y  low i n c i d e n c e  of a t h e r o s c l e r o s i s  w a s  a s s o c i a t e d  w i t h  a c h a n g e  in 
s e r u m  f a t t y  a c i d  p a t t e r n  i n  f a v o u r  of 20:5 a n d  a s u b s e q u e n t  c h a n g e  i n  P C / T X  f o r m a t i o n  i n  

f a v o u r  of T X A 3 / P G I 3  ( 5 ) .  



Increased platelet aggregation associated with a disturbed prostaglandin/thromboxane 

formation has been shown i n  diabetics with vascular disorder (8). We have recently shown 

that diabetic children have a diminished vascular response to post-ischaemic hyperaemia 

(6). This response i s  t o  a major part dependent on PGI2 formation (6). A f i r s t  step i n  
studying these interactions i s  a description of the serum fatty acid composition i n  a group 

of diabetic children without atherosclerosis or diabetic vascular disease compared with 

the pattern i n  healthy matched controls, which i s  the aim of this work. 

SUBJECTS 

The study comprised 28 children aged 4 to 17 years (17 girls and I 1  boys) with insulin 
dependent diabetes mellitus (IDDM). The height, body weight and growth velocity were i n  

a l l  cases within 22 SD for Swedish children (12). None of the children had albuminuria, 

hypertension or ophthalmological or other clinical signs of vascular disease. They were 

being treated with two doses of intermediate monocomponent porcine insulin daily. Some 

of them were also receiving a rapid monocomponent insulin i n  the morning and/or 

afternoon. Their total daily insulin dosage was 0.5 - 1.2 IU/kg body weight. They were a l l  
treated according t o  the same general principles, including prescriptions of regulated diet, 

aiming at a fat consumption of 30-33% of the energy intake and a P/S 

(polyunsaturated/saturated) ratio of about 0.5. Judging from clinical and laboratory 

findings the diabetic disease was under good control (haemoglobin A1 10.8+1.8%, fasting 

serum glucose 9.6L0.5 mmol/l, serum triglyceride concentations (TG) 0.7220.23 mmol/l, 

and cholesterol concentrations (chol) 4.59'0.78 mmolf I. Thirteen of the diabetic children 

had peers of the same age and sex, living i n  the same area and most often attending the 

same class a t  school, participating as matched healthy controls. This study i s  part of an 

investigation approved by the Ethical Committee of the Medical Faculty of the University 

of Uppsala. 

METHODS 

A l l  blood specimens were taken fasting at 08.00-08.30 in the morning before breakfast 

and insulin injection. Serum glucose and H b A l  were determined by routine methods 

(Yellow Spring Instruments 23 AM glucose analyzer and H b A l  microcolumns, Bio-Rad 

Laboratories). TG and chol in serum were determined by semiautomated methods in an 

LKB system (2071, 2074, 20861, using commercial test kits (Test Combination from 

Boehringer-Mannheim and Nyco-test cholesterol from Nyegaard). The concentrations of 

serum apolipoproteins (apo) B, A-I and A-I1 were determined by electroirnmunoassay using 

monospecific antibodies as earlier described i n  detail (21). 

The fatty acid compositions of serum triglycerides (TG) cholesterol esters (CE) and 

phospholipids (PL) were determined in blood serum. The blood samples were allowed to 
coagulate for two hours and serum was collected by low speed centrifugation at +4OC. The 

112 



s e r u m  lipids w e r e  e x t r a c t e d  w i t h  c h l o r o f o r m - m e t h a n o l  a n d  s e p a r a t e d  by t h i n  l a y e r  

c h r o m a t o g r a p h y  a c c o r d i n g  to a m e t h o d  previously d e s c r i b e d  (I). T h e  fatty a c i d s  of t h e  

i s o l a t e d  lipid f r a c t i o n s ,  t r i g l y c e r i d e s ,  c h o l e s t e r o l  e s t e r s  a n d  phospholipids, w e r e  

t r a n s e s t e r i f i e d  to m e t h y l  e s t e r s  (17) a n d  s e p a r a t e d  i s o t h e r m a l l y  at 185OC o n  a 10% SP- 
2340 c o l u m n  in a P y e  U n i c a m  104 gas-liquid c h r o m a t o g r a p h  e q u i p p e d  w i t h  a n  a u t o m a t i c  

s a m p l e  i n j e c t o r  ( H e w l e t t  P a c k a r d  Co.) R e t e n t i o n  t i m e s  of known f a t t y  a c i d  s t a n d a r d s  

(Supelco inc.,) w e r e  used f o r  i d e n t i f y i n g  t h e  p e a k s  of t h e  c h r o m a t o g r a m  (9). T h e  r e l a t i v e  
c o m p o s i t i o n s  of t h e  d i f f e r e n t  i d e n t i f i e d  f a t t y  a c i d s  ( e x p r e s s e d  in %) a n d  t h e i r  r e t e n t i o n  

t i m e s  w e r e  c a l c u l a t e d  by a H P  3380A d i g i t a l  i n t e g r a t o r .  
T h e  s t a t i s t i c a l  c a l c u l a t i o n s  w e r e  p e r f o r m e d  by t h e  SAS statistical p r o g r a m  p a c k a g e  on 

I B M  155-158 a t  U p p s a l a  University. In c o m p a r i s o n s  b e t w e e n  d i a b e t i c s  a n d  n o n - d i a b e t i c s  
only p a t i e n t s  w i t h  m a t c h e d  c o n t r o l s  w e r e  included a n d  t e s t e d  a g a i n s t  t h e i r  c o n t r o l s  in 

t w o - t a i l e d  p a i r e d  t-tests. When c o r r e l a t i o n s  within t h e  d i a b e t i c  g r o u p  w e r e  p e r f o r m e d ,  a l l  

t h e  28 d i a b e t i c  s u b j e c t s  w e r e  included. 

RESULTS 

TABLE 1: R e l a t i v e  c o n c e n t r a t i o n  of f a t t y  a c i d s  a n d  P I S  r a t i o s  in s e r u m  lipid e s t e r s  of 1 3  
d i a b e t i c  c h i l d r e n  c o m p a r e d  w i t h  t h e i r  m a t c h e d  h e a l t h y  c o n t r o l s  ( m e a n  5 SD), (* = ~ ~ 0 . 0 5 ,  
* *  = p<O.OI). 

14:O 

16:O 

16:l 

I8:O 
18:l 
18:2 

18.3 
20:3 
20:4 

20:5 

P I S  

C E  

C o n t r o l s  D i a b e t i c s  

0.850.2 0.720.2 

11.951.9 11.451.0 

3.551.02 2.950.4* 

1.050.2 1.050.7 
20.623.0 18.051.6 ** 
56.455.9 59.953.0 * 
1.151.1 0.720.8 
0.850.7 0.720.7 

3.651.4 4.22 I ,  3 * 
0.520.5 0.721.1 

C o n t r o l s  

2.450.8 
26.555.3 

5.151.4 

4.651.5 
43.022.7 

15.524.9 
1.750.7 

0.450.7 
0.820.5 
0.050. I 

T G  

D i a b e t i c s  

1.750.7 
25.321.9 

4.620.9 

4.650.9 

41.252.4 
19.352.9 * 
1.850.5 

0.220.3 
1.2+0.6** 
0 . 050 . 0 

4.551.0 5.050.6* 0.550.2 0.720.1 

P L  

C o n t r o l s  D i a b e t i c s  

0.450.1 0.350.1 

32.854.4 32.754 .O 
0.450.4 0.520.3 

16.352.2 15.552.3 * 
13.751.8 12.321.4 * *  
24.154.1 25.623.5 * 
0.820.5 0.520.3 * * 
4.351.5 4.620.6 
6.421.7 7.35 1.8 * * 
0.951.4 0.720.7 

0.651.1 0.720.1 * * 

T h e  f a t t y  a c i d  c o m p o s i t i o n  of C E ,  T G  a n d  P L  of t h e  d i a b e t i c  c h i l d r e n  a n d  t h e i r  c o n t r o l s  

a r e  given i n  T a b l e  1 .  T h e  m o s t  s t r i k i n g  d i f f e r e n c e s  b e t w e e n  d i a b e t i c s  a n d  c o n t r o l s  w e r e  

f o u n d  w i t h i n  t h e  l o n g  c h a i n e d  u n s a t u r a t e d  f a t t y  acids. T h e  l i n o l e i c  a c i d  (18:2) a n d  20:4 
c o n t e n t  in all lipid f r a c t i o n s  w e r e  s i g n i f i c a n t l y  higher in t h e  d i a b e t i c s  t h a n  i n  t h e  c o n t r o l s .  



18:2 in C E  w a s  t h u s  a b o u t  60% in d i a b e t i c s  c o m p a r e d  w i t h  56% in t h e  controls. O n  t h e  

o t h e r  hand, o l e i c  a c i d  (18:l) a n d  linolenic a c i d  (18:3) w e r e  s i g n i f i c a n t l y  l o w e r  in d i a b e t i c s  

in C E  a n d  PL. T h e  18:2/18:1 r a t i o  was significantly higher in d i a b e t i c s  in a l l  s e r u m  lipid 
e s t e r s .  T h e  P / S  r a t i o  w a s  higher in P L  a n d  CE. 

T h e  d e g r e e  of d i a b e t i c  c o n t r o l ,  m e a s u r e d  as H b A l ,  w a s  n o t  significantly c o r r e l a t e d  to 

t h e  f a t t y  a c i d  c o n t e n t  of a n y  lipid f r a c t i o n .  

T h e  c o n c e n t r a t i o n  of a p o  A-I in s e r u m  of t h e  d i a b e t i c  children was significantly 

positively c o r r e l a t e d  to t h e  c o n t e n t  of homo-gamma-linolenic a c i d  (20:3), 20:4 and t h e  
r a t i o  18:2/18:1 and n e g a t i v e l y  c o r r e l a t e d  to t h e  c o n t e n t  of 18:l in t h e  t r i g l y c e r i d e  
f r a c t i o n  while no s u c h  c o r r e l a t i o n  w a s  s e e n  in C E  o r  PL. T h e  c o n c e n t r a t i o n  of s e r u m  a p o  

A-I1 w a s  d i r e c t l y  c o r r e l a t e d  to t h e  c o n t e n t  of in 20:3 TG a n d  t o  t h e  r a t i o  20:3/20:4 in C E  
and TG. T h e  c o n c e n t r a t i o n s  of s e r u m  t r i g l y c e r i d e s  w e r e  inversely c o r r e l a t e d  t o  t h e  
c o n t e n t  of 20:4 in P L  a n d  d i r e c t l y  c o r r e l a t e d  to t h e  20:3/20:4 r a t i o  in t h e  s a m e  f r a c t i o n .  

T h e  s e r u m  c h o l e s t e r o l  was n e g a t i v e l y  c o r r e l a t e d  with t h e  c o n t e n t  of 20:5 in PL. T a b l e  2. 

Within t h e  group of h e a l t h y  c o n t r o l s  t h e r e  w e r e  no s i g n i f i c a n t  c o r r e l a t i o n s  b e t w e e n  t h e  

a p o  A-I c o n c e n t r a t i o n  a n d  any f a t t y  a c i d  c o n c e n t r a t i o n  . T h e  s e r u m  c o n c e n t r a t i o n  of a p o  
A-I1 a n d  a p o  R w e r e  significantly n e g a t i v e l y  c o r r e l a t e d  t o  t h e  c o n t e n t  of 14:O in TG. 

T A B L E  2: C o r r e l a t i o n s  b e t w e e n  p l a s m a  lipid a n d  apolipoprotein c o n c e n t r a t i o n s  a n d  t h e  
r e l a t i v e  c o n c e n t r a t i o n  of s o m e  f a t t y  a c i d s  in s e r u m  lipid e s t e r s  of 28 d i a b e t i c  
children.Only t h e  s i g n i f i c a n t  c o r r e l a t i o n s  a r e  presented.. 

TG vs PL 20:4 

P L  20:3/20:4 
Chol vs P L  20:5 

APO A-I vs TG 18:l 
20:3 

20:4 

18:2/18:1 

a p o  A-I1 v s  C E  20:3/20:4 

TG 20:3 
T G  20:3/20:4 

r = -0.52 
r = +0.56 
r = -0.53 

r = -0.55 

r = +0.54 

r = +0.50 

r = +0.51 
r = +0.60 
r = +0.62 

r = +0.57 

p co.01 

p C O . 0 1  
p <0.01 

p CO.01 

p co.01 

p <0.01 

p co.01 

p <0.001 

p <0.001 

p co.01 

DISCUSSION 

A r e g u l a t e d  d i e t  is t h e  basis f o r  a l l  t r e a t m e n t  p r o g r a m m e s  f o r  d i a b e t e s  mellitus. During 

r e c e n t  y e a r s  t h e  high fat, low c a r b o h y d r a t e  d i e t  h a s  been abandoned in f a v o u r  of a d i e t  
c o n t a i n i n g  a high a m o u n t  of c o m p l e x  c a r b o h y d r a t e s  w i t h  a r e l a t i v e l y  low fat c o n t e n t .  
With r e g a r d  t o  t h e  d i e t a r y  f a t t y  a c i d s  t h e  r e l a t i v e  c o n t e n t  of p o l y u n s a t u r a t e d  fats should 

b e  m o d e r a t e l y  i n c r e a s e d  (1 5). 
T h e  h e a l t h y  c o n t r o l s  showed a proportion of linoleic a c i d  which w a s  similar to t h a t  



e a r l i e r  r e p o r t e d  i n  a n  u r b a n  p o p u l a t i o n  of h e a l t h y  Swedish c h i l d r e n  (13). T h e  h i g h e r  
c o n t e n t  of P U F A  in t h e  s e r u m  lipid e s t e r s  in t h e  d i a b e t i c  c h i l d r e n  r e f l e c t s  t h e  d i e t a r y  
a d v i c e  given. T h e  f a t t y  a c i d  c o n t e n t  of t h e  t r i g l y c e r i d e s  m e r e l y  m i r r o r s  t h e  fat 

composition of t h e  d i e t  d u r i n g  t h e  d a y s  p r e c e d i n g  t h e  test, while t h e  c h a n g e  of t h e  f a t t y  

a c i d  p a t t e r n  in t h e  c h o l e s t e r o l  e s t e r s  a n d  phospholipids i s  m o r e  g r a d u a l  o v e r  a period of 

s e v e r a l  w e e k s  (2). 
In t h e  p r e s e n t  s t u d y  t h e r e  w a s  n o  s i g n i f i c a n t  c o r r e l a t i o n  b e t w e e n  t h e  d e g r e e  of d i a b e t i c  

c o n t r o l  a n d  t h e  f a t t y  a c i d  p a t t e r n  in t h e  s e r u m  lipid e s t e r s .  Assuming t h a t  t h e  P / S - r a t i o  i n  

t h e  s e r u m  lipids is c o r r e l a t e d  to t h e  d i e t a r y  a d h e r e n c e ,  t h i s  i n d i c a t e s  t h a t  t h e r e  w a s  no 

significant r e l a t i o n s h i p  b e t w e e n  t h e  d e g r e e  of d i e t a r y  a d h e r e n c e  a n d  t h e  d e g r e e  of 

d i a b e t i c  c o n t r o l .  H o w e v e r ,  t h i s  d o e s  c e r t a i n l y  n o t  m e a n  t h a t  t h e  d i e t a r y  a d h e r e n c e  i s  of 
no i m p o r t a n c e  f o r  t h e  d i a b e t i c  c o n t r o l .  R a t h e r ,  t h e  l a c k  of c o r r e l a t i o n  m a y  b e  d u e  to t h e  

fact t h a t  t h e  d i a b e t i c  c o n t r o l  i s  i n f l u e n c e d  n o t  only by t h e  fat q u a l i t y  of t h e  d i e t  b u t  a l s o  
by o t h e r  p r o p e r t i e s  of t h e  d i e t  as w e l l  as by t h e  a d m i n i s t r a t i o n  of e x o g e n o u s  insulin. 

A new f i n d i n g  w a s  t h e  p o s i t i v e  r e l a t i o n s h i p  b e t w e e n  t h e  s e r u m  c o n c e n t r a t i o n  of a p o  A-I 

and t h e  r e l a t i v e  c o n t e n t  of p o l y u n s a t u r a t e d  fat a n d  t h e  P / S - r a t i o  in t h e  s e r u m  

triglycerides. A p o  A-I i s  t h e  m a j o r  p r o t e i n  c o m p o n e n t  of t h e  high d e n s i t y  l i p o p r o t e i n s  (11). 
Insulin d e p e n d e n t  d i a b e t i c  c h i l d r e n  h a v e  h i g h e r  A-I c o n c e n t r a t i o n s  t h a n  r n a t c h e d  h e a l t h y  

controls (7). In s p i t e  of high HDL l e v e l s  t h e  i n c i d e n c e  of a t h e r o s c l e r o t i c  v a s c u l a r  d i s e a s e  
in d i a b e t i c s  is high. I t  h a s  b e e n  p o s t u l a t e d  t h a t  t h e  H D L  c o m p o s i t i o n  m a y  b e  q u a l i t a t i v e l y  
d i f f e r e n t  in d i a b e t i c s  c o m p a r e d  w i t h  t h a t  of h e a l t h y  c o n t r o l s  (4). T h e  p o s i t i v e  c o r r e l a t i o n  

between t h e  a p o  A-I c o n c e n t r a t i o n  a n d  t h e  c o n t e n t  of p o l y u n s a t u r a t e d  fat i n  T G  m a y  

indicate s u c h  a d i f f e r e n c e .  In n o n - d i a b e t i c s  a high i n t a k e  of p o l y u n s a t u r a t e d  fats h a s  b e e n  
shown to d e c r e a s e  t h e  s e r u m  a p o  A-I l e v e l s ,  a t  l e a s t  d u r i n g  s h o r t  t e r m  d i e t a r y  t r e a t m e n t  

(19, 20). T h e  l a c k  of c o r r e l a t i o n  b e t w e e n  t h e  s e r u m  a p o  A-I v a l u e s  a n d  t h e  P / S - r a t i o  in t h e  

other s e r u m  lipid e s t e r s  in t h i s  s t u d y  i n d i c a t e s  t h a t  t h e  A-I c o n c e n t r a t i o n  w a s  n o t  r e l a t e d  

t o  t h e  i n t a k e  of p o l y u n s a t u r a t e d  fats d u r i n g  longer t i m e  periods. T h e  p o s i t i v e  c o r r e l a t i o n  

between A-I a n d  t h e  c o n t e n t  of P U F A  in t h e  s e r u m  t r i g l y c e r i d e s  i n d i c a t e s  a p o s i t i v e  

relationship b e t w e e n  t h e  p o l y u n s a t u r a t e d  d i e t a r y  f a t  i n t a k e  d u r i n g  t h e  l a s t  d a y s  b e f o r e  

t h e  s a m p l e  w a s  t a k e n  a n d  t h e  s e r u m  a p o  A-I levels. Possibly a high i n t a k e  of P U F A  
mirrors a high total fat i n t a k e .  I n t r o d u c t i o n  of n e u t r a l  fat in t h e  i n t e s t i n e  i n d u c e s  
synthesis of a p o  A-I i n  t h e  i n t e s t i n a l  c e l l s  (18). 

We h a v e  e a r l i e r  d e s c r i b e d  a p o s i t i v e  r e l a t i o n s h i p  b e t w e e n  t h e  s e r u m  a p o  A-I1 
c o n c e n t r a t i o n  a n d  t h e  s e r u m  t r i g l y c e r i d e  c o n c e n t r a t i o n  in d i a b e t i c  c h i l d r e n  (7). T h e  

present s t u d y  s h o w s  t h a t  b o t h  A-I1 a n d  T G  a r e  d i r e c t l y  c o r r e l a t e d  to t h e  r a t i o  20:3/20:4 in 

t h e  s e r u m  lipid e s t e r s .  T h e  T G  c o n c e n t r a t i o n  w a s  i n v e r s e l y  c o r r e l a t e d  w i t h  20:4 i n  TG. W e  
have no e x p l a n a t i o n  f o r  t h e s e  f i n d i n g s  o r  f o r  t h e  n e g a t i v e  c o r r e l a t i o n  b e t w e e n  t h e  s e r u m  

cholesterol c o n c e n t r a t i o n  a n d  t h e  20:5 c o n t e n t  i n  PL. 

O n e  m a i n  f i n d i n g  in t h e  p r e s e n t  s t u d y  w a s  t h e  c o n f i r m a t i o n  of t h e  d i f f e r e n c e  b e t w e e n  

d i a b e t i c  c h i l d r e n  a n d  h e a l t h y  c o n t r o l s  w i t h  r e g a r d  to t h e  r e l a t i o n s h i p s  b e t w e e n  s e r u m  

apolipoprotein c o n c e n t r a t i o n s  a n d  s e r u m  lipid c o m p o s i t i o n .  W e  h a v e  e a r l i e r  shown 

I I5 



diverging relationships in insulin t r e a t e d  d i a b e t i c  children and h e a l t h y  c o n t r o l s  b e t w e e n  

s e r u m  apolipoprotein c o n c e n t r a t i o n s  a n d  s e r u m  lipid c o n c e n t r a t i o n s  (7). T h i s  s t u d y  shows 

t h a t  t h e  t w o  groups d i f f e r  a l s o  with r e g a r d  to t h e  relationships b e t w e e n  s e r u m  

apolipoprotein c o n c e n t r a t i o n s  a n d  t h e  f a t t y  a c i d  composition of t h e  s e r u m  lipid e s t e r s .  

This is c o m p a t i b l e  with t h e  view t h a t  n o t  only t h e  q u a n t i t y  b u t  a l s o  t h e  q u a l i t y  of t h e  
s e r u m  lipoproteins a r e  d i f f e r e n t  in t h e s e  t w o  c a t e g o r i e s  of children (4). 

ACKNOWLEDGEMENT 

This s t u d y  was s u p p o r t e d  by g r a n t s  f r o m  AB NOVO, Malmo, Sweden a n d  by t h e  Swedish 
M a r g a r i n e  Industrial Association f o r  Nutritional-Physiological R e s e a r c h .  

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REFERENCES 

Boberg, J.: S e p a r a t i o n  of labelled p l a s m a  a n d  t i s s u e  lipids by thin l a y e r  
Chromatography. - A q u a n t i t a t i v e  m e t h o d o l o g i c a l  study. C l i n  C h i m  A c t a  14:325-334, 
1966. 
Boberg, J., G u s t a f s s o n ,  I-!3., K a r l s t r o m ,  B., Lithell, H., Vessby, B. & Werner, I.: 
E f f e c t  of a d i e t  e n r i c h e d  in p o l y u n s a t u r a t e d  f a t t y  a c i d s  on h y p e r l i p o p r o t e i n e m i a  in 
man. Rheinisch-Westfalische A k a d e m i e  d e r  Wissenschaften 63:XI-87, 1978. 
Dayton, S., P e a r c e ,  M.L., Hashimoto, S., Dixon, W.J. & Tomayasu, U.: A c o n t r o l l e d  
c l i n i c a l  t r i a l  of a d i e t  high in u n s a t u r a t e d  fat in p r e v e n t i n g  c o m p l i c a t i o n s  of 
atherosclerosis. A m  H e a r t  Association, Monograph 25, C i r c u l a t i o n  XL, Suppl 11, 1- 
63, 1969. 
Durrington, PN.: S e r u m  high d e n s i t y  lipoprotein c h o l e s t e r o l  in d i a b e t e s  mellitus. An 
An analysis of f a c t o r s  which i n f l u e n c e  i t s  c o n c e n t r a t i o n .  Clin C h i m  A c t a  104:ll-23, 
1980. 
Dyerberg, J., Bang, H.O., Stoffersen,E., Moncada, S. & Vane J.R.: E i c o s a p e n t a e n o i c  
a c i d  a n d  p r e v e n t i o n  of t h r o m b o s i s  a n d  a t h e r o s c l e r o s i s ?  L a n c e t  2:117-119, 1978. 
Ewald, U., Tuvemo, T. & Rooth, G.: E a r l y  r e d u c t i o n  of v a s c u l a r  r e a c t i v i t y  in 
d i a b e t i c  children d e t e c t e d  by t h e  t r a n s c u t a n e o u s  oxygen e l e c t r o d e .  L a n c e t  1: 1287- 
1288, 1981. 
Ewald, U., Tuvemo, T., Vessby, B. & Wfilinder, 0.: S e r u m  a p o l i p o p r o t e i n s  A-I, A-I1 
a n d  B in d i a b e t i c  children a n d  m a t c h e d  h e a l t h y  controls. A c t a  P a e d i a t r  Scand 71:15- 
18, 1982. 
Halushka, P.V., Lurie, D. & Colwell, J.A.: I n c r e a s e d  synthesis of prostag1andin-E- 
l i k e  m a t e r i a l  by p l a t e l e t s  f r o m  p a t i e n t s  w i t h  d i a b e t e s  mellitus. N Engl J Med 

Horning, E.C., Ahrens, J r .  E.H., Lipsky, S.R., Mattson, F.H., Meal, J.G., T u r n e r ,  
D.A. & G o l d w a t e r ,  W.H.: Q u a n t i t a t i v e  a n a l y s i s  of f a t t y  a c i d s  by gas-liquid 
c h r o m a t o g r a p h y .  J Lipid R e s  5:20-27, 1964. 
Houtsmuller, A.J., van Hal-Ferwerda, J., Zahn,K.J. & Henkes, H.E.: F a v o u r a b l e  
i n f l u e n c e s  of linoleic a c i d  o n  t h e  progression of d i a b e t i c  micro- a n d  
macroangiopathy. N u t r  M e t a b  24 (Suppl I): 105-1 18, 1980. 
J a c k s o n ,  R.C., M o r r i s e t t ,  J.D. & G o t t o ,  A.M. Jr.: Lipoprotein s t r u c t u r e  and 
metabolism. Physiol R e v  56:259-316, 1976. 
Karlberg, P., T a r a n g e r ,  J., E n g s t r o m ,  I. et al.: T h e  s o m a t i c  d e v e l o p m e n t  of c h i l d r e n  
in a Swedish urban c o m m u n i t y .  A p r o s p e c t i v e  longitudinal study. I. P h y s i c a l  g r o w t h  
f r o m  b i r t h  to 16 y e a r s  a n d  longitudinal o u t c o m e  of t h e  s t u d y  during t h e  s a m e  a g e  
period. A c t a  P a e d i a t r i c  S c a n d  Suppl 258:7-76, 1976. 
Knuiman, J.T., West, C.E., Hermus, R.J.J. & H a u t v a s t ,  J.C.A.J.: F a t t y  a c i d  
composition of c h o l e s t e r o l  e s t e r s  in s e r u m  in boys f r o m  16 developing and developed 
countries. A t h e r o s c l e r o s i s  3 7 6  17-624, 1980. 
L e r e n ,  P.: T h e  effect of plasma c h o l e s t e r o l  lowering d i e t  in m a l e  survivors of 
m y o c a r d i a l  i n f a r c t i o n .  A c o n t r o l l e d  c l i n i c a l  t r i a l .  A c t a  Med S c a n d  Suppl 466:l-92, 
1966. 

297: 1306-1310, 1977. 



15 
16 

17 
18 

19 

20 

21 

Mann, J.I.: D i e t  and diabetes. Diabetologia 18:89-95, 1980. 
Miettinen, M., Turpeinen, O., Karvonen, M.J., Elosuo, R. & Paavilainen, E.: E f f e c t  
of c h o l e s t e r o l  lowering d i e t  on m o r t a l i t y  from coronary h e a r t  disease and o t h e r  
causes. L a n c e t  ii:835-838, 1972. 
O f f i c i a l  Methods of Analysis, 10th AOAC, Washington DC, Sect. 26.052, 429, 1965. 
Schonfeld, G., Bell, E. & Alpers, E.: Intestinal apoproteins during fat absorbtion. J 
Clin Invest 61:1539-1550, 1978. 
Shepherd, B., Packard, C.J., P a t s c h ,  J.P., C o t t o ,  A.M. 3. & Taunton, O.D.: E f f e c t s  
of polyunsaturated fat on t h e  properties of high density lipoproteins and t h e  
metabolism of apoprotein A-I. J Clin Invest 61:1582-1592, 1978. 
Vessby, B., Gustafsson, I-B., Boberg, J., Karlstrom, B., Lithell, H. & Werner, I.: 
Substituting polyunsaturated f o r  s a t u r a t e d  fat as a single change in a Swedish diet: 
E f f e c t s  on serum lipoprotein metabolism and glucose t o l e r a n c e  in p a t i e n t s  with 
hyperlipoproteinaemia. Europ J Clin Invest 10: 193-202, 1980. 
Vessby, B., Lithell, H., Hellsing, K., Ostlund-Lindqvist, A-M., Gustafsson, I-B., 
Boberg, J. & Ledermann, H.: E f f e c t s  of B e z a f i b r a t e  on t h e  serum lipoprotein lipid 
and apolipoprotein composition, lipoprotein triglyceride removal c a p a c i t y  and t h e  
fatty acid composition of t h e  plasma lipid esters. Atherosclerosis 37:257-269, 1980. 

Received J a n u a r y  31, 1982. 
Address f o r  reprints: 
T o r s t e n  Tuvemo, M.D. 
D e p a r t m e n t  of P a e d i a t r i c s  
University Hospital 
S-750 14 Uppsala 

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