B Tripathy

J P Das

K C Samal

S K Das

Sidhartha Das

CiteSeerX

December, 1984 15 
CORONARY HEART DISEASE, DIABETES AND CIRCULATING 
LIPOPROTEIN CHOLESTEROL 
 
*Sidhartha Das, **B, B. Tripathy, ***K. C. Samal, ****S. K. Das and *****J. 
P. Das 
 
Introduction 
 
Coronary heart disease (CHD) and stroke have been recognised to be responsible for 
more than 50 percent of deaths in the developed countries of the Westl. The former 
ranks first as the major killer and is the protean clinical outcome of autherosclerotic 
occlusive vascular disease (ASVD)1,2. Atherosclerosis develops both faster and more 
extensively in diabetics than in general population3. ASVD, CHD in particular, is not 
only the commonest complication of diabetes mellitus but also accounts for nearly 
3/4th of the mortality amongst diabetics3. Lipid abnormalities have been widely 
acknowledged as the prime mechanism promoting accelerated atherosclerosis, more 
so at a premature age 2,4,5. 
 
Till late hypercholesterolaemia was the only recognised risk factor in this regard. But 
recent knowledge, has revealed that distribution of cholesterol among lipoprotein 
fractions (LP) i.e High. density lipoprotein (HDL), Low density lipoprotein (LDL) 
and Very low density lipoprotein (VLDL) correlate better than levels of total plasma 
cholesterol (Tc) perse 4,7,8. Various population studies have shown that an 
independent and inverse correlation exists between cholesterol content of HDL 
(HDLc) and prevalence of CHD 7,9,10. However, hypertriglyceridaemia and raised 
VLDL have been shown to be the most important lipid disorder in diabetics 10,11,12,13. 
Role of these abnormalities as independent risk factors for ASVD, CHD in particular, 
is not yet established5,13,14. The high prevalence of CHD in diabetics could be 
medicated through alterations in the levels of HDLc, but data available so far do not 
contribute to the elucidation of such a mechanism15,16 
 
Thus it was decided to examine in detail LP cholesterol status in cases of premature 
CHD of both diabetic (NIDDM) and non-diabetics along with uncomplicated patients 
of NIDDM, with a view to findout the common lipid key factor either responsible for 
or predisposing to premature CHD. 
 
Materials and Methods 
 
Forty six male patients of CHD below 50 years of age, diagnosed from clinical pre-
sentation, electrocardiography and serum enzyme studies (SGOT & SGPT) reporting 
to the Department of Medicine and Cardiology were included in this study. Eight of 
them were cases of NIDDM and on sulphonylurea therapy for over 5 years. 
Accordingly 20 male patients of NIDDM matched for age and free of any infection, 
vascular or metabolic complications and on sulphonylurea therapy for more than 5 
years were selected from amongst those attending the Endocrine section alongwith 
25 healthy controls matched for age and sex. 
 
*M.D. (Med) Senior Resident Cum Research Associate 
**M.D. (Med), M.D. (Pharm.) P. G. Professor & Head (Ret) Medicine.  
***M.D., D.M. Associate Professor & Head Endocrinology. 
****M D. Junior Teacher, Medicine. 
*****D.M., F.R.C.P., F.A.M.S. Professor & Head of Cardiology. 
Departments of Medicine, Endocrinology & Cardiology, S.C.B. Medical College, 
Cuttack-753007, India. 
December, 1984 16 
 
The patients and controls selected were such that they were comparable from the 
point of views of nutritional status, (2200 to 2300 Kc/day & BM1 - 21 to 24), 
alcohol, intake, smoking and physical activity etc. inorder to avoid interference of 
other known parameters on the LPc profile. The subjects of study were grouped as : 
 
(A) Healthy controls, (B) Non-diabetics with CHD,  
 
(C) Diabetics with CHD & (D) Diabetics without CHD. 
 
Blood samples were collected from each of the patients and controls after an over-
night fast. In case of the CHD patients the samples were collected not later than 24 
hours following diagnosis in hospital. Fractionation of the major lipoproteins in 
plasma was done by the dual precipitation technique of Wilson and Spiger (1973)17. 
Estimation of cholesterol content of each fraction i.e. HDLc, LDLc & VLDLc and 
total plasma cholesterol (Tc) was done by Zak's method (1957).is Plasma 
triglycerides (Tg) was estimated by the method of Van Handel and Zilversmit 
(1957).19 
 
Observations.  
 
A total of 28 diabetics (NIDDM) on sulphonylurea therapy were studied out of which 
8 had CHD. From amongst the 63 non-diabetics, 38 were cases of CHD and rest 
healthy controls. All subjects studied were between 35 to 50 years of age. 
 
As shown in Table-I, the plasma Tc values were similar in both groups of CHD 
patients, but was higher (P< 0.5) in the diabetics without CHD when compared with 
healthy controls (A Vs D). The Tg level was much higher. (P< 0.01) in the non-
diabetics with CHD than healthy controls (A Vs B), so also in the patients of Group 
D than in Group A (PL 0.05). But no such difference could be observed between the 
two groups of CHD cases (B Vs C), while these values were far higher than in 
controls (Table-I). Further, both Tc and Tg levels were similar in the 2 groups of 
diabetics (C Vs D). 
 
Mean HDLc was lower (P< 0.01) and LDLc higher (P< 0.05) in the non-diabetic 
CHD cases than in controls (A Vs B). There was no significant di(l'erence in these 
two parameters either between Groups A & D or Groups C & D. On the contrary 
HDLc value was significantly higher (P< 0.01) in the diabetics with CHD as 
compared to non-diabetics with CHD (B Vs C), but LDLc did not reveal any 
statistical difference. 
 
VLDLc was the only fractional cholesterol value found to be signifcantly higher (P< 
0.01) in both groups of CHD cases (B-30.4 ± 10.9 & C-30.6 ± I5.1 mg/dl) and 
diabetics without CHD (D-34.7 ± 15.2 mg/dl) than in healthy controls (16.60 - 9~0 
mg/dl). 
 
The ratios between the fractional lipoprotein cholesterol and Tc, depicting the 
relative distribution of cholesterol amongst LP, are presented in Table-II. Amongst 
the ratios HDLc/Tc and HDLc/LDLc (which are known to be inversely related to the 
risk of developing (CHD) were much lower (PL 0.01) in the non-diabetics with CHD 
as compared to  
 
 
 
December, 1984 17 
TABLE-I 
Mean Total and Fractional Lipoprotein Chotesterol aed Trtglyceride Levels in 
Controls and Patients 
(in mg/dl) 
 
Group of subjects  HDLc  LDLc VLDL Tc Tg   
 
(A) Healthy controls  68.7  131.0 16.6  216.4 92.3    
  S.D. (±) 15.0  29.0 9.0  31.5 30.9   
(B) Non-diabetics  44.8  166.0 30.4  240.1 127.5   
with CHD S.D. (±) 10.9  45.6 10.9  52.8 46.0   
(C) Diabetics with  68.9  136.6 30.6  236.6 157.5   
CHD S.D. (±) 16.4  33.6 15.1  64 5 45.5   
(D) Diabetics  73.4  146.2 34.7  254.4 143.6   
without CHD S.D. (±) 15.6  39.1 15.2  53.4 53.4     
 
 
Significance of differences 
 
Groups compared HDLc  LDLc VLDLc Tc Tg   
 
A Vs B P< 0.01  P< 0.05 P< 0.01 NS P< 0.01  
A Vs D  NS  NS P< 0.01 P< 0.05 P< 0.05   
B Vs C P< 0.01  NS NS  NS NS   
C Vs D  NS  NS NS  NS NS     
 
NS=not significant 
 
TABLE-II 
Ratios between Fractional I.ipoprntein Cholesterol and Total Cholesterol in 
Patient and Controls 
 
Group of subject HDLc/Tc HDLc/LDLc LDLc/Tc  VLDLc/Tc   
 
(A) Healthy controls 0 32  0.55  0.60  0.08   
    S.D. (+_) 0.06  0.22  0.08  0.04   
(B) Non-diabetics with 0.19  0.29  0.68  0.13   
   CHD S.D. (±) 0.04  0.09  0.08  0.06   
(C) Diabetics with 0.30  0.52  0.58  0.12   
      CHD S.D. (±) 0.06  0.15  0.06  0.04   
(D) Diabetics without 0.30  0.54  0.57  0.13   
    CHD S. D. ( + ) 0.07  0.21  0.07  0.04     
 
Significance of differences 
 
Groups compared HDLc/Tc HDLc/LDLc LDLc/Tc  VLDLc/Tc   
 
A Vs B P< 0.01  P< 0.01 P< 0.01  P< 0.05   
A Vs D NS   NS NS   P< 0.05   
B Vs C P< 0.01  P< 0.01 P< 0.05  NS   
C Vs D NS   NS NS   NS     
 
NS : Not significant.          
December, 1984 18 
 
both healthy controls (A Vs B) and diabetics with CHD (B Vs C). Not only the 
diabetics with CHD had higher HDLc/Tc and HDLc/LDLc but also the diabetics 
without CHD had similar higher ratios and there was no difference in between them 
(C Vs D). LDLc/Tc was higher in Group-B than Group A (P < 0.01) and Group C (P 
< 0.05). Interestingly VLDLc/Tc was the only common parameter raised in both 
groups of diabetics and nondiabetics with CHD when compared with controls 
(Table-II) indicating higher cholesterol content in the VLDL fraction than normal in 
all these three groups of patients. 
 
Discussion  
 
Lipid abnormalities have been shown to be the most important single risk factor in 
the development of ASVD, before the sixth decade of lifel,2,4. Thus this study was 
conducted on subjects below 50 years of age. Reports from the West on lipoprotein 
cholesterol have established that alterations in HDLc and LDLc pesse can predispose 
to accelerated ASVD and premature CHD in the general population7,8,9. However, 
studies on the LPc status in premature CHD cases are sparse in Indian literature. 
Moreover, reports on the LPc profile in patients of NIDDM with CHD are equally 
scanty20 even if it is widely accepted that CHD is more common amongst diabetics 
than in general population. 
 
Our observations of a raised Tg level in the patients of CHD whether diabetic or not 
along with those of Group-D is quite in agreement with most recent reports from 
both within and abroad2l,22. 
 
The significantly lower values of HDLc, HDLc/Tc and HDLc/LDLc and higher 
LDLc in the non-diabetic CHD patients is in keeping with most studies since the 
leading work of Miller and Miller (1975) supports the view that HDLc has an inverse 
relation with the occurance of CHD6,23. Over and above the absolute values of HDLc, 
its relative proportion to Tc and LDLc have been identified to be independently 
predictive of CHD8. Analysis of the ratios obtained from this study (Table-II) 
revealed striking differences between the two groups of CHD patients. 
 
The mean HDLc levels were not found to be different in either group of diabetics 
when compared with controls and parodoxically diabetics with CHD had 
significantly higher (P< 0.01) HDLc than their non-diabetic counterparts (B Vs C). 
 
Rise in HDLc in diabetics consequent to insulin therapy is well documented l2,l5 The 
interesting finding here is that a11 these diabetics were on sulphonylurea therapy for 
periods over 5 years. Therefore, the present consensus that HDLc levels may not be 
lower in NIDDM cases whether on insulin or sulphonylurea24,25 with or without 
CHD20 is borne out of this study. 
 
In view of the above it is difficult to attribute a protective role entirely to HDLc or an 
atherogenic role to LDLc in the pathogenesis of CHD at a premature age. However, 
the observations of a significantly higher VLDLc and VLDLc/Tc in both groups of 
CHD patients and diabetics(with and without CHD)may point to a common 
denominator although levels of Tg and VLDL have not been generally accepted as 
independent risk factors, the update report on the atherogenic potency of a 
cholesterol  rich VLDL  (Beta-VLDL)  by  Mahley26  in  experimental  models  calls  
 
December, 1984 19 
attention to the involvernent of VLDL in this process. Partially metabolised VLDL, 
still rich in cholesterol (Remnant Particles) have also been found to be highly 
atherogenic4,6. Thus the high cholesterol content of VLDL as revealed in the present 
study demands further exploration and may provide a clue to a common lipid key 
factor, responsible for premature ASVD in general. 
 
Summary  
 
Of 46 male patients below 50 years of age, with established CHD, eight were dia-
betics. Plasma lipids viz, triglycerides, total cholesterol as well as cholesterol content 
of major lipoprotein fraction, i.e. HDLe, LDLc and VLDLc were estimated in the 
above along with 25 age matched controls and 20 diabetics without CHD. Both 
groups of diabetics were on sulphonylurea therapy for over 5 years. 
 
Compared to controls non-diabetics with CHD had significantly lower levels of 
HDLc, and higher levels of LDLc, VLDLc and Tg where as there was no difference 
in HDLc and LDLc levels and diabetics with or without CHD, HDLc, HDLc/Tc and 
HDLc/ LDLc were significantly higher (P < 0.01) in diabetics with CHD than in non-
diabetics with CHD. Although VLDLc and VLDLc/Tc were significantly higher in 
diabetics, compared to controls the values were similar in patients of CHD whether 
diabetic or non-diabetic. 
 
These results suggest that higher incidence of premature CHD amongst diabetics is 
unrelated to alternations in levels of HDLc or LDLc, while VLDL with high 
cholesteral content (Beta-VLDL) can not be ruled out as an important risk factor for 
both diabetics and non-diabetics. 
 
References  
 
1. Wolinsky, H. N. Atherosclerosis : In Cecil's Textbook of Medicine, l5th Edn. W. 
B. Saunders & Co (1979), 1218. 
 
2. Bierman, E. L. : Atherosclerosis and other forms of arteriosclerosis : In 
Harrison's Principles of Internal Medicine, 9th Edn. MC Hill Kogakusha Ltd. 
(1980), 1156. 
 
3. Steiner, G: Diabetes and Atherosclerosis. An overview; Diabetes (1981), 30 
(2):1. 
 
4. Lewis, B.: Hyperlipidaemia and cardiovascular disease: In Recent Advances in 
Medicine, Vol. 17, Editors : Baron, D. N. Compton, N, and Dawson, A. M. ; 
Churchill Livingstone (1977), 246 
 
5. Fielding, C.J. : The endothelium, triglyceride-rich lipoproteins and 
atherosclerosis : Insights from cell biology and lipid metabolism : Diabetes 
(1981), 30 (2) : 19. 
 
6. Goldstein, J. L., Hazzard, W. R., Schrott, H. G. et al : Hyperlipidaemia in 
Coronary Heart Disease. The Jr. Clin. Invest. (1973), 52 : 1533. 
 
7. Miller, G. J. and Miller, N. E. : Plasma high density lipoprotein concentration 
and development of ischaemic heart disease; Lancet (1975), 1 : 16. 
 
December, 1984 20 
8. Streja, D. Steiner, G. and Kwiterovich, P. O. : Plasma high density lipoproteins 
and ischaemic heart disease : Ann. Inter. Med. (1978), 89 : 871. 
 
9. Miller, N. E., Thelle, L. S., Forde, C. H. and Mios, O. D. (The Tromso Heart 
Study, High density lipoprotein and coronary heart disease. A Prospective case 
control study. Lancet (1977), 1 : 965. 
 
10. Gordon, T., Castell, W. P., Hjortland, M. C. et al : High density lipoprotein as a 
protective factor against coronary heart disease. The Framingham Study : Am. 
Jr. Med. (1977), 62 ; 707. 
 
11. Steiner, G., Poapart. M., Davidson, J. K. : Production of chylomicrons like 
lipoproteins from endogenous lipids by intestine and liver of diabetic dogs; 
Diabetes (1975), 24 : 263. 
 
12. Nikkila, E. A. and Hormila, P : The serum lipids and lipoproteins in insulin 
treated diabetics : Diabetes ( 1978), 27 : 1078. 
 
13. Nikkila, E. A. : High density lipoprotein in diabetes. Diabetes (1981), 30 (2) : 82. 
 
14. Hulley, S. B., Rosenman, R H., Bawol, R. D. et al : Epidemiology as a guide to 
clinical decision; the association between trigiyceride and coronary heart disease; 
New Eng. Jr. Med (1980), 302 : 1383. 
 
15. Cohen, A. H., Fidel, J., Cohen, B et al : Diabetes, Blood lipids, Lipoproteins and 
changes in environment; Restudy of the "New emigrant Yemenites in Israel" : 
Metabolism` 1979, 28 : 728. 
 
16. Eckel, R. H., Albers, J; Chaung, M. C. et al : High density lipoprotein 
composition in insulin dependent diabetes mellitus : Diabetes, (1981), 30 : 132. 
 
17. Wilson, D. E. and Spiger, H. J. : A dual precipitation method for quantitative 
plasma lipoprotein measurement without ultracentrifugation : J. Lab. Clin. Med. 
(1973), 82 : 473. 
 
18. Zak, B. Simple and rapid microtechnique for serum cholesterol: Amer. Jr. Clin, 
Path. (1957), 27 : 336. 
 
19. Van Handel, B and Zilversmit, B. D. : Micro method in the direct estimation of 
serum triglycerides; Jr. Lab. Clin. Med. (1957), 60 : 152. 
 
20. Taskinen, R., Nikkila, E. A., Harno, K. et al : Serum lipoproteins in insulin 
treated with and without coronary heart diseases; Abstract-11th Congress I. D. F. 
: Excerpt. Medica (1982), 577 : 102. 
 
21. Misra, K. P., Suresh, S., Balchandran, N. et al Cholesterol contents of plasma 
lipoproteins with symptomatic peripheral vascular disease : Ind. Heart Jr. (1980), 
23 (1) : 1. 
 
 
 
 
 
December, 1984 21 
 
 
22. Misra, K. P., Suresh, S. Subramaniam, R. Et al : Correlation between plasma 
lipoprotein cholesterol and evaluated coronary atherosclerosis, Abstract-
International Congress on Tropical Cardiology, Ind. Heart Jr. (1982), 34 (5) : 
300. 
 
23. Das, Sidhartha, Das J. P., Das, S. K. et al : Lipoprotein Cholesterol and 
Triglyceride in patients of coronary heart disease under 50 years of age, 
Abstract-International Congress on Tropical Cardiology. Ind. Heart Jr. (1982), 
34 (5) : 318. 
 
24. Paisey, R., Eckoles, R. S. Hambley, J. et al. The effect of cholorpropamide and 
insulin on serum lipids, lipoproteins and fractional triglyceride remove : 
Diabetologia (1978) 15 : 81. 
 
25. Das, Sidharth, Tripathy, B B and Samal K. C. : Plasma lipids and lipoprotein 
cholesterol in diabetics on insulin and sulphonylurea therapy. Abstract-Annual 
Conference of the Diabetic Association of India 1983 (Submitted for 
publication). 
 
26. Mahaley, R. W. : Cellular and molecular biology of lipoprotein metabolisrn in 
atherosclerosis : Diabetes (1981), 30 (2) : 60, 
 
 
 


CORONARY HEART DISEASE, DIABETES AND CIRCULATING LIPOPROTEIN CHOLESTEROL

http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=7895CD593736B3FF43BA4912B91690FB?doi=10.1.1.1050.1114&rep=rep1&type=pdf

CORONARY HEART DISEASE, DIABETES AND CIRCULATING LIPOPROTEIN CHOLESTEROL

Abstract

Similar works

Full text

Available Versions

CiteSeerX