Study of serum lipids in leprosy

Introduction

The literature is replete with many studies related to the lipid composition of various mycobacteria. Though Virchow first thought that vacuolisation of foam cells in leprosy was a hydropic change, it was soon established that the contents are made up of lipids.[1] Imaeda et al,[2] opined that lipids inside the lepra cells may be of host origin, which may therefore result in alterations in serum lipids in patients of leprosy. Moreover, ability to synthesize different lipid moieties and their distribution to various body tissues through plasma seems to be altered in leprosy.[3] Low incidence of atherosclerosis and coronary heart disease in patients of leprosy has been related to elevation of HDL cholesterol and reduction of total cholesterol in patients with high bacterial Indices.[3] Recently it has been suggested that cholesterol dynamics in macrophages might harbour the secrets of cultivation of M. leprae,[13] Furthermore, no study has been done correlating the lipid profile with the type of leprosy and the bacterial load. Hence the present work.

Meterials and Methods

Fifty, fresh and untreated cases of leprosy formed the study group. Fifty age and sex matched healthy individuals constituted the controls. All patients were subjected to clinical, bacteriological, immunological (lepromin) test and histopathological investigations as per the criteria laid down by Ridley and Jopling.[4] After an overnight fast, 5 ml of venous blood was drawn and clear sera obtained by centrifugation was used for biochemical investigations. Triglyceride level was estimated by the enzymatic color test GOP-PAP method (Merck system), total cholesterol was estimated after enzymatic hydrolysis and oxidation (Merck system). Low Density Lipoprotein (LDL), Very Low Density Lipo protein (VLDL) and chylomicrons were precipitated by polyanions in the presence of metal ions to leave HDL cholesterol in solution. The precipitates were used for determining the levels by enzymatic methods.[5] The liver function tests were carried out in all patients.

Results

In all, there were 32 males and 18 females in the study group. The male, female ratio being 1.77:1. Of these 50 patients, one had tuberculoid leprosy, 21 borderline tuberculoid, 12 borderline borderline, 7 borderline lepromatous and 9 had lepromatous leprosy. Fifty age and sex matched healthy individuals formed the controls and the lipid values in controls are dioicted in [Table - 1].

Lipid profile in TT patient

In the present study only one case had TT leprosy. The serum triglyceride was 79%, total cholesterol was 135%, HDL cholesterol was 27.5 mg%, LDL cholesterol was 91.7mg% and VLDL cholestrol was 15.8 mg%. The bacterial index was zero in this patient.

Lipid profile in BT patients

Twenty-one patients belonged to BT group in the present study. The lipid levels along with the bacterial indices are shown in [Table - 2]. The value of serum triglycerides ranged from 39-128 mg%, total cholesterol ranged from 90-217 mg%, HDL cholesterol ranged from 19. 2-24.3 mg%, LDL cholesterol ranged from 42.7-158.5 mg% and VLDL cholesterol ranged from 9-25.6 mg%. As evident from the table, three of these BT patients had bacterial index of one plus.

Lipid profile in BB patients

In the present study, 12 belonged to the BB group. The lipid profile as well as bacterial indices are depicted in [Table - 3]. The serum triglyceride levels ranged from 36-55 mg%, total cholesterol ranged from 99-229 mg% and VLDL cholesterol ranged from 7.2-51 mg%. Four of these patients had bacterial index of one plus, 3 had 2+, whereas 5 had index of 3+.

Lipid profile in BL patients

In the present study, 7 patients belonged to the BL group. The profile and the bacterial indices are shown in [Table - 4]. The serum triglyceride levels ranged from 33-151 mg%, total cholesterol ranged from 86-169 mg%, HDL cholesterol ranged from 20.5-67 mg%, LDL cholesterol, ranged from 53.6-115.3 mg%, VLDL cholesterol ranged from 6.6-30.2 mg%. Five patients in this group had a bacterial index of 3+ and 2 had an index of 4+.

Lipid Profile in LL patients

In the present study, 9 patients belonged to the LL group. The lipid profile and the bacteriological indices are shown in [Table - 5]. The serum triglyceride levels ranged from 56-207 mg%, total cholesterol ranged from 113-227 mg%, HDL cholesterol ranged from 12.7-37.4 mg%, LDL cholesterol ranged from 62.7-158 mg% and VLDL cholesterol level ranged from 11.2-41 mg%. Three patients showed a bacterial index of 4+, 2 had an index of 5+ and 4 showed an index of 6+.

Liver function tests

No significant alteration was observed in the values of serum proteins, SCOT and SGPT in any patient in the present study.

Discussion

The ability to synthesize different lipid moieties and their distribution through plasma to all the body tissues seems to be altered in leprosy.[3]

Some research workers have attempted to study the biochemical alterations including the study of lipid metabolism as a guide to early diagnosis.[6] Furthermore, lipids may also play an important role as an etiological agent in various vascular abnormalities seen in leprosy. Thus the study of lipid metabolism in leprosy is of great significance as the lipid metabolism is the hub of pathology of leprosy and cholesterol dynamics in macrophages might harbour the secrets of cultivation of M. leprae.[3] Moreover, very few studies are available in the literature about the various lipid fractions and their correlation with the type of leprosy or bacterial indices in individual patients.

An increase in serum triglyceride level had been documented by Misra et al,[7] on the otherhand Bansal et all observed a decrease in mean level in their series. In the present study the value in one TT case was low but not so low statistically as compared to controls. In the BT patients, the values were within normal range as compared to controls. In BB group of patients also, the level of serum triglyceride showed no significant alterations when cimpared to normal controls. In BL and LL patients in the present study, minimal elevation in the values was abserved, but it was not statistically significant. However, Bensal et al[8] in their work found a lowering in the levels of serum triglyceride in multibacillary patients.

Ahaley et al,[3] have documented lowered serum cholesterol levels in patients of leprosy. On the other hand, Gokhale and Godbole[9] observed higher levels in their study. In their present work, ther level of serum cholesterol in TT patient was 135 mg% which is low but not so low statistically. In BT group of patients, the values were decreased in 13 out of 21 cases. The decrease was not related to the bacterial load and could be due to disease per se. It could be due to increase in levels of cytokines such as TNF[10] leprosy. In BB group of patients, the level of total cholesterol was statistically decreased in 6 out of 12 cases. Bansal et al,[8] also found decrease in the levels in multibacillary cases in their study group. The level of total cholesterol in LL group of patients in the present study was decreased in 7 out of 9 patients and the decrease was statistically significant. This observation is in agreement with the finding of Sritharan et al[11] who stated that in active LL, free fatty acids are increased which exerts an inhibitory effect on hepatic lipogenesis directly and indirectly on cholesterol synthesis by inhibiting pyruvate dehydrogenase enzymes of the liver. This in turn could explain low lipid level in LL group.

The level of HDL cholesterol in TT patient was within normal range as compared to controls. In the BT group, the level was decreased in 8 out of 21 patients and the decrease was statistically significant. It had been postulated that this could be due to increase in the levels of cytokines such as tumor necrosis factor which lowers the HDL level. Bansal et alb also found lower levels in paucibacillary patients. In the BB group of patients, the level of HDL cholesterol was not significantly altered. In the BL group, the level was decreased in 3 out of 7 patients, the level was decreased in 6 out of 9 cases and the decrease was statistically significant. Sritharan et al,[11] opined that the decrease could be explained by the decreased adrenocortical functions in LL patients which may result in decreased activity of lipogenic and glycolytic enzymes. However, Bansal et al,[8] found significant increase in the values of HDL cholesterol in multibacillary patients in their series.

The level of LDL cholesterol in TT patient was with in normal range. In BT group of patients, the level was increased in 2 out of 21 cases and the increase was statistically significant. As explanined above, an increase in the level of cytokines could explain the significant increase in the level in these 2 BT cases. In the BB group, the level was decreased statistically in 2 of the 12 cases.

In BL patients, the level was significantly decreased in 3 out of 7 patients and in LL group the level was statistically decreased in 2 of the 9 cases. Sitharan et al,[11] also observed a decrease in the level of LDL cholesterol in active LL patients.

Very Low Density Lipoprotein cholesterol has not been studied in detail in leprosy. In the present study, the level was with in the normal range in the TT patients. In the BT group also, the values were within normal range as compared to the controls. In the BB group of patients, the level was raised in 3 out of 12 patients, but was not statistically significant. Seven patients belonged to the BL group. The level of VLDL cholesterol in this group also was within the normal range. However, in LL patients the level was increased in one out of 9 cases, but was not significant statistically.

The documented studies on the serum values of lipids in leprosy have shown contrary and conflicting observations. An increase in serum triglyceride has been reported by Misra et al,[7] while Bansal et alb have reported a decrease in their values. Similarly, mostauthors,[8] have reported decrease in the level of total cholesterol and our findings are in agreement with them. Like wise, Ahaley et al[3] observed an increase in the level of HDL cholesterol in patients with high bacterial indices while Bansal et al[8] found such increase in both pauci-as well as multibacillary leprosy patients. In the present study, HDL cholesterol values were significantly low in BT and LL patients.

Sritharan et al,[11] and Ahaley et al,[3] have documented decreased values of LDL cholesterol in leprosy, moreso in LL groups. In the present study also, decreased values were observed in BT, BB, BL and LL groups and the decrease was statistically significantly reduced.

The values of VLDL cholesterol in leprosy has not been studied adequately in the past. Ahaley et al,[3] have documented that the level was decreased, moreso in LL groups and patients with high bacterial indices. On the other hand Bonsai et al,[8] did not observe any significant change in either pauci-or multibacillary patients. In the present study, values of VLDL cholesterol were within normal range in TT and BT leprosy. In BB group it was insignificantly raised in 3 of 12 patients and in BL the level was within normal range in all 7 cases. In LL group it was again insignificantly raised in one out of 9 patients.

Several studies have been documented in the leterature on the influence of hepatic involvement on the lipid levels. Gupta and Gupta,[12] opined that the liver is the principal organ involved in the lipid metabolism and therefore its invasion by lepra bacilli may alter the lipid metabolism. However, Ramu and Nagarajan,[3] opined that liver function studies in leprosy do not suggest physiopathological changes to implicate liver. In the present study also, the liver function tests were found to be within normal range in all the patients.

In the final analysis, although there is close similarity between the foamy cells of leprosy and macrophages of other diseases, which store lipids, the serum level of various lipid fractions in leprosy in the present study was not in consonance with the extent of the disease process. It is possible that the stored lipids from foamy cells are not released into the circulation and also that the bacillemia of lepromatous leprosy produces no measurable effect on serum lipids.

Similarly, no correlation was observed in the present study between the levels of different lipid fractions in the sera, the type of leprosy or the bacterial indices in the study groups.