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  IN THIS Article
 ::  Introduction
 ::  Material and methods
 ::  Results
 ::  Discussion
 ::  Acknowledgement
 ::  References

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Year : 1983  |  Volume : 29  |  Issue : 4  |  Page : 193-200

Plasma lipids and lipoproteins in treated diabetics.







How to cite this article:
Retnam V J, Nerurkar S V, Gupte M H, Bhandarkar S D, Taskar S P. Plasma lipids and lipoproteins in treated diabetics. J Postgrad Med 1983;29:193-200


How to cite this URL:
Retnam V J, Nerurkar S V, Gupte M H, Bhandarkar S D, Taskar S P. Plasma lipids and lipoproteins in treated diabetics. J Postgrad Med [serial online] 1983 [cited 2019 Dec 10];29:193-200. Available from: http://www.jpgmonline.com/text.asp?1983/29/4/193/5512




  ::   Introduction Top

Abnormalities of plasma lipids and lipoproteins have been documented in untreated and treated diabetics by Indian[14], [15] and foreign workers.[3], [8], [9], [13], [19] The hyperlipidemias (HL) and the hyperlipoproteinemias (HLP') have been implicated as risk factors in atherosclerotic disease, particularly ischemic heart disease. Whether correction of an existing HL or HLP would help in either primary or secondary prevention of myocardial infarction is debated.[11] However, prevention or correction of a known risk factor is sound medicine. It is, therefore, essential to decide the optimum form of treatment of diabetes mellitus which would be associated with complete absence or lowest prevalence of HL and HLP. Hence, a study of the prevalence of HL and HLP in diabetics on different treatment regimes, attending the Department of Endocrinology, K.E.M. Hospital, was undertaken.

  ::   Material and methods Top

One hundred and fifty-two adult onset diabetics on the register of the Diabetes Clinic of the Department of Endocrinology were chosen for the study. They were on different modes of treatment. These patients were regularly attending the clinic once in three months for at least one year before inclusion in the study, so that they could be classified as controlled or uncontrolled. For the purpose of the study, the poorly controlled and the moderately controlled diabetics according to the Joslin Clinic criteria[16] were pooled together as uncontrolled (82 cases); those who were well controlled according to the Joslin Clinic criteria were labelled as controlled (70 cases). Each patient was subjected to a detailed physical examination, ECG and routine blood biochemistry. Patients with associated major organ disease (heart, lung, kidney, liver, thyroid or brain) were not included in the study. Sixty-three apparently healthy subjects (41 men and 22 women), aged 40-60 years, who were either hospital employees or patients with minor ailments, attending the medical outpatient department, acted as the normal controls.
Venous blood for lipid and lipoprotein analyses was collected in EDTA in the fasting state, using the protocol described by Rifkind[23] (no recent change in diet or weight; no recent acute illness; no lipid lowering or lipid influencing drugs). The plasma was immediately separated by centrifugation at 3000 r.p.m. at room temperature. All analyses were started on the same day as the blood collection. Total cholesterol was estimated by Abell's method,[1] total triglycerides by Van Handel and Zilversmit's method,[27] and lipoprotein electrophoresis on agarose gel by Nobel's method.[21] The agarose gel slides were stained with Sudan Black B and scanned using Joyce Lobel Chromoscan Model No. 201. The total cholesterol and triglycerides were expressed as mg per 100 ml of plasma and the lipoprotein fractions as relative percentages.
The values in the normal controls were analysed statistically and a value 2 S.D.s above the mean for each parameter was set as the cut off point between the normal and the abnormal for the purpose of this study. Using these cut off points, the data in the diabetic patients on different modes of treatment were analysed for the prevalence of HLP (Fredrickson's classification as modified by WHO).[4] Further, the mean of each parameter in controlled patients, uncontrolled patients and the combined (controlled + uncontrolled) group of patients on different modes of treatment was compared statistically with that in normal controls, using two-tailed, unpaired, Student's `t' test.
The same plasma samples were analysed for lipid composition of the lipoprotein fractions. These data are being reported in a separate publication.[20]

  ::   Results Top

[Table - 1] shows the distribution of the study subjects according to the age and the treatment regime at the time of study. One hundred and twenty-eight patients were receiving a sulphonylurea, chlorpropamide in most instances, alone or in combination with either phenformin or insulin. By contrast, 56 patients were on insulin, either alone or with a sulphonylurea. Only 14 patients were being treated with diet alone. The youngest patient was 32 years old and the oldest 78 years old. There were 83 men and 69 women in this study. The data of men and women were pooled, as otherwise the subgroups would be too small for statistical analysis. The patients were on a conventional, Indian, high-carbohydrate, moderate protein, low-fat diet. A previous, similar study[22] had demonstrated the following pattern (Mean ± S.D.) of calorie, carbohydrate, fat and protein intake in 80 diabetics (36 men and 44 women) attending the clinic: calories 1397 ± 416; carbohydrate.234.6 ± 74.8 g; fat 28.5 ± 11.9 g; and protein 50.9 ± 16.4 g. The diet history had been recorded by the recall method.
[Table - 2] shows the means and standard deviations of different parameters in normal controls, controlled diabetics, uncontrolled diabetics, and in the combined (controlled + uncontrolled) group of diabetics. As seen from the table, the mean values of most of the parameters in all the three groups of patients were significantly higher than those in the normal controls.
[Table - 3] shows the cut off limits between the normal and the abnormal values of different parameters. [Table - 4] shows the prevalence of different types of HLP in controlled and uncontrolled diabetics on different treatment regimes. These figures were obtained using the cut off values shown in [Table - 3]. Sixty-eight patients had HLP of one type or another. The commonest was type IV (32 subjects), followed by type II b (24 subjects). The maximum clustering of patients with HLP was in subjects on a sulphonylurea alone (35/57 patients). Patients on sulphonylurea + phenformin combination or sulphonylurea + insulin combination did have type IIb and type IV HLP, but type IIa HLP was distinctly uncommon in them. Patients on insulin appeared to have the lowest prevalence of any type of HLP. Finally, whereas 20 out of 70 controlled diabetics had HLP, 48 out of 82 uncontrolled diabetics had it (p < 0.001).
[Table 5] shows the values (means and standard deviations) of total cholesterol, total triglycerides, and alpha, prebeta, and beta lipoproteins in normal controls, controlled diabetics, uncontrolled diabetics and in the combined (controlled + uncontrolled) group of diabetics on different treatment regimes. As the primary purpose of this study was to find out which mode of treatment gave results closest to those observed in normal controls [Table 5] indicates only those comparisons where the results are not statistically significant even at the 5170 level (i.e., p > 0.05). The other comparisons gave results which were statistically significant at least at the 5% level. As the table shows, results closest to those in the normal controls were seen in patients well controlled on diet and in patients on insulin. Patients on a sulphonylurea, con. trolled as well as uncontrolled, showed significant differences from the normal controls in almost all the parameters. However, cholesterol levels in patients controlled with either sulfonylurea + phenformin or sulfonylurea + insulin combination were not significantly different from those in the normal controls. But, even in these two groups, beta lipoprotein levels were significantly higher than those in normal controls.

  ::   Discussion Top

This study showed that HLP was present in 20 out of 70 controlled diabetics and in 48 out of 82 uncontrolled diabetics. The lowest frequency of HLP was in patients on insulin and the highest in patients on sulfonylureas [Table - 4] Phenformin seemed to protect patients only from Type Ha HLP, whereas insulin seemed to protect the patients from all types of HLP. When the means of the individual parameters in patients on different treatment groups were compared with those in normal controls, it was again brought out that patients on insulin tended to have values closest to those of normal controls. As a combined group, diabetics had values of all parameters significantly different from those in normal controls [Table - 2]
UGDP study[16] demonstrated that there was no difference in the proportion of patients having blood cholesterol over 250 mg% in their five treatment groups. Carlson and Ostman[9] found that during short term treatment, chlorpropamide caused a reduction in elevated levels of plasma triglycerides along with reduction in hyperglycemia. On the other hand, Belknap et al[5] found that in spite of improved blood glucose control there was no reduction in either plasma cholesterol or triglyceride levels in tolbutamide treated patients. Szucs and Csapo[24] found that whereas 78% of diabetics treated with insulin had their total serum lipids below 1500 mg%, only 54% of those treated with carbutamide had similar values. Bennion and Grundy[6] reported that insulin caused significant reduction of cholesterol and triglyceride levels in diabetics. Michael et al[18] demonstrated in a small number of patients that insulin caused improvement in plasma cholesterol and triglyceride levels in diabetics. Chandalia et al[10] found a significant fall of triglycerides in diabetics treated with dietary restriction and oral antidiabetic drugs, but not in those who were treated with insulin; in their study, serum cholesterol did not diminish in any of the three groups. Phenformin has been reported to reduce plasma cholesterol[24] and triglycerides[25] in diabetics. Ahrens et al[2] suggested that a high carbohydrate diet might cause hypertriglyceridemia; but Bierman and Hamlin[7] demonstrated that high carbohydrate diet produced a transient rise followed by reduction in plasma triglyceride levels in diabetics. Vishwanathan et al[28] demonstrated that a high-carbohydrate, high fibre diet caused a reduction in both plasma cholesterol and triglyceride levels in diabetics.
The reader will thus see that there is no unanimity of opinion in the literature about the effect of antidiabetic treatment, particularly the oral hypoglycemic agents, on the serum lipids and lipoproteins. Recent work with continuous subcutaneous insulin infusion (CSII) has demonstrated that during such treatment the serum lipids return to normal levels.[12] However, the safety of CSII with the open loop system currently in use has been questioned. Under these circumstances the next best might be intermittent insulin administration as is being practised in most centres.
The interpretation of the above laboratory findings in terms of ischemic hear[disease must await further studies in the clinic. In the meanwhile. the authors would hesitate to recommend universal treatment of the adult onset diabetics with insulin, at least in countries like India, where insulin is in short supply and is expensive when available. The authors feel that the adult onset diabetics would face the consequences of treatment with drugs other than insulin only after long periods of time, measurable in years. But, the universal use of insulin in adult onset diabetics would mean denial of insulin to the juvenile diabetics who would succumb to non-availability of insulin almost immediately. This fact should not be lost sight of by the diabetologists who must choose their priorities carefully and wisely.

  ::   Acknowledgement Top

We thank the Dean, Seth G.S. Medical College and K.E.M. Hospital, for allowing us to publish this hospital data.

  ::   References Top

1.Abell, L. L., Levy, B. B., Brodie, B. B. and Kendall, F. E.: A simplified method for the estimation of cholesterol. J. Biol. Chem., 195: 357-366, 1952.  Back to cited text no. 1    
2.Ahrens, E. H . , Hirsch, J . , Oette, K . , Farquhar, J. W. and Stein, Y.: Carbohydrate-induced and fat-induced lipemia. Trans. Assoc. Amer. Phys., 74: 134-136, 1961.   Back to cited text no. 2    
3.Ballantyne, D., White, C., Strevens, E. A., Lawrie, T. D. V., Lorimer, A. R.. Manderson, W. G. and Morgan, H. G.: Lipoprotein concentrations in untreated adult onset diabetes mellitus and the relationship of fasting plasma triglyceride concentration to insulin secretion, Clin. Chim. Acta, 78: 323-329, 1977.  Back to cited text no. 3    
4.Beaumont, J. L., Carlson, C. A., Cooper, G. R., Fejjar, Z., Fredrickson, D. S. and Strasser, T.: Classification of hyperlipidemias and hyperlipoproteinaemias. Bull. World Hlth. Org., 43: 891-1001, 1970.  Back to cited text no. 4    
5.Belknap, B. H., Bagdade, J. D., Amaral, J. A. P. and Bierman, E. L.: Plasma lipids and mild glucose intolerance. IIA double-blind study of the effect of tolbutamide and placebo in mild adult diabetic outpatients. In "Tolbutamide after ten years." Editors: W. J. H. Butterfield and W. Van Westerning, Proceedings of the Brook Lodge Symposium, Augusta, Michigan. March 6-7, 1967. Excerpts Medics Foundation Publication, New York, 1967, p. 171.  Back to cited text no. 5    
6.Bennion, L. J. and Grundy, S. M.: Effect of diabetes mellitus on cholesterol metabolism in man. New Engl. J. Med., 296: 1365-1371, 1977.  Back to cited text no. 6    
7.Bierman, E. L. and Hamlin, J. T.: The hyperlipemic effect of low-fat, highcarbohydrate diet in diabetic subject's. Diabetes, 10: 422'-437, 1961.  Back to cited text no. 7    
8.Bowers, C. Y., Muldrey, J. E. and Hamilton, J, G.: Blood lipid and glucose levels of patients with diabetes mellitus treated with chlorpropamide. Amer. J. Med. Sci., 247: 676-681, 1964.  Back to cited text no. 8    
9.Carlson, L. A. and Ostman, J.: Effect of chlorpropamide treatment on serum lipid levels in diabetes mellitus. Acts Med. Scand., 170: 561-564, 1961.  Back to cited text no. 9    
10.Chandalia, H. B., Ajgaonkar, J. and Talwalkar, N. G.: Lipid profile in diabetes mellitus. (Abstract): In, "Current Topics in Diabetes Research." Abstracts of IX Congress of the International Diabetic Federation, New Delhi, India, October 31-November 5, 1976, pp. 58-59.   Back to cited text no. 10    
11.Dollery, G. T.: Arterial hypertension. In, "Cecil's Text Book of Medicine," 16th Ed. Edited by J. B. Wyngaarden and L. H. Smith, W. B. Saunders & Co. Philadelphia, 1982, p. 223-239.  Back to cited text no. 11    
12.Dunn, F. L., Pietri, A. and Raskin, P.: Plasma lipid and lipoprotein levels with continuous subcutaneous insulin infusion in Type I diabetes. Ann. Intern. Med., 95: 426-431, 1981.  Back to cited text no. 12    
13.Garcia, M. J., McNamara, P. M., Cordon, T. and Kannell, W. B.: Morbidity and mortality in diabetics in Framingham population. Sixteen year follow up. Diabetes, 23: 105-111, 1974.  Back to cited text no. 13    
14.14. Gupta, M. M., Suri, K. K. and Chakravarti, A. K.: Serum lipids and hyperlipoprotainaemia in uncontrolled diabetics. J. Diab. Assoc. India, 19: 149-153, 1979.  Back to cited text no. 14    
15.Jain, A. P. and Gupta, O. P., Study of blood lipids in diabetes without any manifest vascular complications. J. Diab. Assoc'. India, 20: 29-34, 1980.  Back to cited text no. 15    
16.Klimt, C. R., Knatterud, G. L., Meinert, C. L. and Prout, T. E.: University Group Diabetes Programme: A study of the effects of hypoglycemic agents on vascular complications in patients with adult onset diabetes. I-Design, methods and base line results. Diabetes, 19: 7477&93, 1970.  Back to cited text no. 16    
17.Krall, L. P.: The oral hypoglycemic agents. In, "Joslin's Diabetes Mellitus". 11th Ed. Editors: A. Marble, P. White, R. F. Bradley and L. P. Krall, Lea and Febiger, Philadelphia, 1971, pp. 302-338.   Back to cited text no. 17    
18.Michael, B., Camejo, M., Jacobs, J., Parkar, J., Cry M. St, and Ruderman, N. B.: HDL in diabetes. Lancet 1: 155, 1979.  Back to cited text no. 18    
19.Morris, J. H., West, D. A. and Bolinger, R. E.: Effect of oral sulfonylurea on plasma triglycerides in diabetes. Diabetes, 13: 87-89, 1964.  Back to cited text no. 19    
20.Nerurkar, S. V., Retnam, V. J., Taskar, S. P. and Bhandarkar, S. D.: Lipid composition of lipoproteins in treated diabetics. J. Postgrad. Med., 24: 201211, 1983.  Back to cited text no. 20    
21.Nobel, R. P.: Electrophoretic separation of plasma lipoproteins in agarose gel. J. Lip. Res., 9: 693-700, 1968.  Back to cited text no. 21    
22.Retnam, V. J.: Serum lipoproteins in diabetes mellitus, M.D. Thesis, Bombay University, Bombay, 1978.  Back to cited text no. 22    
23.Rifkind, B. M.: Lipoproteins and hyperlipoproteinemia Clinics in Endocrinology and Metabolism: 2: 3-10, 1973.   Back to cited text no. 23    
24.Schwartz, M. J., Mirsky, S. and Shaeffer, L. E.: Phenformin, serum lipids and diabetes mellitus. Lancet, 1: 959, 1965.   Back to cited text no. 24    
25.Szucs, S. and Csapo, G.: Serum total lipid and lipoprotein fractions in diabetic patients treated with insulin or carbutamide. Amer. J. Med. Sci., 246: 710713, 1963.  Back to cited text no. 25    
26.Stout, R. W. and Bierman, E. L.: The lipid lowering effect of phenformin in hypertriglyceridemia. The role of insulin. and free fatty acids. Diabetes, 21(suppl. 1): 380, 1972.  Back to cited text no. 26    
27.Van Handel, E. and Zilversmit, D. B.: Micromethod for determination of triglycerides. J. Lab. and Clin. Med., 50: 152157, 1957.  Back to cited text no. 27    
28.Vishwanathan, M., Snehalata, C., Ramchandran, A. and Shobha, R.: The effect of calorie-restricted, high-carbohydrate, high-protein, low-fat diet on serum lipids in diabetes, J. Assoc. Phys. India, 26: 162-168, 1978.  Back to cited text no. 28    

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