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542)

Serum Fructosamine and Lipid Profile in Children with Malignant Diseases Orkide Donma, M.D., Fusun Atlihan, M.D., Mehmet Ali Tas, M.D., M. Metin Donma, M.D. Department of Biochemistry, Medical Faculty, Cukurova University,Adana, and Department of Pediatrics, Medical Faculty, Dicle University, Diyarbakir, Turkey

Serum levels of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and fructosamine (FA) were determined in thirty -three children with malignant diseases and twenty healthy controls aged 1-14 years. Of them, FA was the parameter measured in children with malignancy for the first time. Mean serum TC, HDL-C, LDL-C and FA showed statistically significant decreases in malignancy compared to healthy children, whereas a statistically significant increase was observed for TG concentrations in serum. From these data, we conclude that significant relations between serum lipids and lipoproteins and the state of malignancy exist in the children studied, and it should be remembered that serum FA concentrations are affected by abnormal serum protein turnover when one deals with any type of neoplastic disease. Key Words Fructosamine, Lipids, Malignancy

Introduction It is apparent that malignant lymphomas and leukemias share a number of clinical and biological features. Their ability to mimic other diseases is almost unlimited. The role of biochemistry in evaluating these patients is much more complex than in solid tumors [ l ] . Biochemistry contributes to diagnosis by measuring the concentration of certain constituents in blood, serum and urine. Currently, many biochemical procedures have been applied for this purpose [ l ] . However, there are still some parameters, such as fructosamine, which have not yet been tried. In this article, we have attemptReceived March 11, 1990 Accepted June 8, 1990 Correspondence address: Orkide Donma, M.D., Biochemistry Department, Medical Faculty, Cukurova University, PK 49 Gar/Adana, Turkey.

ed to examine the effect of some biochemical procedures such as fructosamine, lipid profile and lipoprotein analysis on the investigation and management of patients with these diseases.

Patients and Methods Thirty-three children with malignant diseases (Hodgkin’s disease, non-Hodgkin lymphoma, acute myeloblastic leukemia, acute lymphoblastic leukemia, etc.) and twenty healthy children aged 1-14 years were studied. The children with malignant diseases were untreated before. Blood samples were collected after an overnight fast. Total cholesterol (TC) and triglycerides (TG) in serum were determined by enzymatic methods [2, 31. High density lipoprotein cholesterol (HDL-C) analysis was also performed by the enzymatic total cholesterol method, using the commercially available HDL-C precipitant, phosphotungstic acid [4] .

Serum fructosamine and lipid profile (63) 541 Low density lipoprotein cholesterol (LDL-C) values were calculated using the Friedewald formula [5] . Lipoprotein electrophoresis was performed on the serum samples to determine the percentages of lipoprotein fractions. FA concentrations were estimated by means of Johnson’s modified nitro-blue tetrazolium (NBT) method [6]. Absorbance readings for FA analysis were taken in a Shimadzu W-VIS 260, a microcomputer-controlled, thermostatcontrolled, recording double-beam spectrophotometer with CRT display and graphic recorder. Data are expressed as mean 5 SE and range. Statistical analysis was performed by the Student t-test.

Results The mean? SE values and ranges for serum lipid fractions (TC, TG, HDL-C, LDL-C) and FA concentrations of the children with malignant diseases and the control group are shown in Table 1. TC, HDL-C and LDL-C values obtained for the children with malignancy were significantly lower than those observed for the control group, whereas TG concentrations were significantly higher in the malignancy group when compared to the controls. We also observed that the decrease found in FA concentrations in the malignancy group was statistically significant.

Discussion Serum fructosamine is a reliable index of

glycemia over the preceding 1 to 3 weeks. It is assumed that both concentration and turnover rate of serum proteins do not differ from those in the reference population so as to affect the degree of protein glycation. However, this is not the case when serum albumin concentrations are lower than 30g/l [6-81. It has been reported that patients with abnormal rates of serum protein turnover also have FA concentrations significantly different from those of the reference population. For this purpose, Lloyd and Marple have chosen thyrotoxicosis and hypothyroidism as their respective models for increased and decreased serum protein turnover [8]. In some investigations, serum FA was not significantly influenced by the albumin concentration in the serum, but increased catabolism and abnormal plasma protein ratios where the mean half-life is decreased, may signify that this measurement represents an integration of blood glucose during the preceding 21 days [ 7 ] . The results tabulated in Table 1 show a statistically significant decrease in serum FA concentrations in the children with neoplastic diseases compared to the controls. This difference may not reflect changes in the protein or glucose concentrations in serum, but presumably results from increased protein metabolism. Plasma lipid abnormalities have been reported in many animal tumors [9, 101. Spiegel and colleagues examined serum lipid and lipoprotein concentrations in twenty-five patients with unspecified acute leukemia or non-Hodgkin lymphoma [ I 11. All had an ab-

Table 1. Serum total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and fructosamine Concentrations in children with malignant diseases and healthy controls Group

TC (mmol/L)

HDL-C (mmol/L)

LDL-C (mmol/L)

TG (mmol/L)

FA (mmol/L)

Malignancy

Mean f SE Range

4.45 0.21 1.27-7.72

*

0.81 f 0.09 0.03-2.05

2.76 t 0.19 0.08-6.27

1.90 f 0.16 0.80-4.37

1.9 f 0.1 1.3-2.8

Controls

Mean f SE Range

5.15 k 0.18 3.51 - 6.19

1.53 i 0.05 1.09 - 1.98

3.30 1.82

1.14 0.17

2.4 1.5

p Q 0.01

p Q 0.01

P

Vol. 32 No. 5 October 1990

f

0.22

- 5.59

p Q 0.05

f

0.11

- 2.09

p < 0.01

i

0.1

- 2.7

p Q 0.01

542 (64) Donma et a1

normality in at least one plasma lipid fraction. It was also reported that hyperlipidemia in leukemia may be more prevalent than previously realized [ 121 . This study consists of thirty-three children with malignancy, aged 1-14 years. We have observed significantly higher serum TG and significantly lower TC, HDL-C, LDL-C and FA concentrations in the children with malignancy compared to the control group. We have obtained extremely low HDL-C concentrations, especially in children with non-Hodgkin lymphoma. The observed values for this group were between 0.21-0.31 mmol/L. One child with acute lymphoblastic leukemia had 0.03 mmol/L of HDL-C. Lipoprotein electrophoresis patterns confirmed the relation between the percentage of alpha fraction and HDL-C concentrations. Most of our patients had almost no alpha fraction in their electrophoretic patterns. Upon examination, it was observed that these were the samples in whch HDL-C levels varied between 0.03-0.52 mmol/L. A survey of the literature on cellular and circulating lipids and our results suggest that alterations in lipid metabolism may give information on tumor burden and act as chemical markers of malignancy in the leukemias. We also conclude that FA results for patients in whom there is likely to be abnormal serum protein turnover must be cautiously interpreted.

References 1. Goldberg DM, Brown D. Critical review. Biochemical tests in the diagnosis, classification and management of patients with malignant lymphoma and leukemia. Clin Chim Acta 1987; 169: 1-76. 2. Total Cholesterol, CHOD-PAP method, Wako Chemicals GmbH. 3. Triglyceride N-FA, GPO-PAP method, Wako Chemicals GmbH. 4. HDL-Cholesterol, phosphotungstic acid method, Boehringer Mannheim GmbH. 5. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma without the use of the preparative centrifuge. Clin Chem 1972; 18: 499-502. 6. Johnson RN, Metcalf PA, Baker JR. Relationship between albumin and fructosamine concentration in diabetic and non-diabetic sera. Clin Chim Acta 1987; 164: 151-162. 7. Seng LY, Staley MJ. Plasma fructosamine is a measure of all glycated proteins. Clin Chem 1986; 32: 560. 8. Lloyd D, Marples J. Serum fructosamine and thyroid function. Clin Chem 1986; 32: 1985. 9. Kralovic RC, Zepp A, Cenedella RJ. Studies of the mechanism of carcass fat depletion in experimental cancer. Eur J Cancer 1977; 13: 10711079. 10. Kannan R, Wilson L, Baker N. The role of dietary fat and hepatic triglyceride secretion in cancer-induced hypertriglyceridemia. Lipids 1978; 887-891. 11. Spiegel RJ, Schaeffer EJ, Magrath IT, Edwards BK. Plasma lipid alterations in leukemia and lymphoma. Am J Med 1982; 72: 775-782. 12. Blackett PR, Koren E, Blackstock R, Downs D, Wang C-S. Hyperlipidemia in acute lymphoblastic leukemia. Ann Clin Lab Sci 1984; 14: 123-129.

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