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Determination of Free L-Carnitine Levels in Type II Diabetic Women with and Without Complications

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Determination of Free L-Carnitine Levels in Type II Diabetic Women with and Without Complications European Journal of Clinical Nutrition (2007) 61, 892–895 & 2007 Nature Publishing Group All rights reserved 0954-3007/07 $30.00 www.nature.com/ejcn ORIGINAL ARTICLE Determination of free L-carnitine levels in type II diabetic women with and without complications A Poorabbas1, F Fallah1, J Bagdadchi2, R Mahdavi2, A Aliasgarzadeh3, Y Asadi2, H Koushavar2 and M Vahed Jabbari2 1Ilam Medical University, Ilam, Iran; 2Faculty of Nutrition, Tabriz Medical University, Tabriz, Iran and 3Tabriz Medical University, Tabriz, Iran Background: Studies on the determination of carnitine levels and nutritional status in patients of type II diabetes. Objective: We designed this study to determine changes of serum-free L-carnitine in type II diabetic women. Design: A cross-sectional study (case–control study). Setting: Clinical of Endocrinology and Metabolism, Sina Hospital, Pharmacological Research Center, Tabriz Medical university, Iran. Patients and methods: Taking into account the importance of the control of diabetes, in the present case-control study, the levels of serum-free L-carnitine, blood glucose and lipids, systolic and diastolic blood pressure, body mass index (BMI) and nutritional status assessed in the case and control groups which were selected by the simple sampling method. The control group (n ¼ 18) included patients with no complications and the case group (n ¼ 33) was grouped into three subgroups including patients with retinopathy, hyperlipidemia and neuropathy. Results: Study results indicated that the mean serum-free L-carnitine concentration in the case group was significantly lower than its mean concentration level in the control group, 39.6378.99 vs 53.4270.93 mmol/l, respectively (Po0.001). Serum-free L-carnitine in retinopathy, hyperlipidemia and neuropathy case subgroups were 39.0379.89, 39.6378.99 and 40.44712.50 mmol/l, respectively (P40.05). No significant difference was found between the serum-free carnitine levels of the case subgroups. The mean blood glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, very low- density lipoprotein cholesterol levels and systolic and diastolic blood pressure were significantly higher in the case group than in the control group. Conclusion: In this study, the mean serum-free L-carnitine levels in diabetic patients with complications was almost 25% lower than in diabetic patients with no complications. On the basis of the study results, carnitine supplementation in diabetic patients, especially in patients with diabetes complications, might be useful. European Journal of Clinical Nutrition (2007) 61, 892–895; doi:10.1038/sj.ejcn.1602594; published online 21 February 2007 Keywords: free carnitine; diabetes complications Introduction renal diseases), the relation of glycemia to macrovascular disease in type II diabetes is more modest (ADA, 2003). There Diabetes mellitus is often accompanied by dyslipidemia and are studies that have reported abnormal carnitine metabo- dysfunction in glucose and protein metabolism (Marc et al., lism in diabetes (Williamson et al., 1992). 2005). Type II diabetes is associated with a two- to fourfold The synthesis of L-carnitine requires two essential amino excess risk of coronary heart disease (CHD). Although the acids (lysine and methionine), iron (Fe2 þ ), and vitamins C, degree of glycemia in diabetic patients is strongly related to B6 and niacin in the form of nicotinamide dinucleotide the risk of microvascular complications (retinopathy and (NAD) (Seim et al., 2001). Carnitine is synthesized primarily in the liver and also in the kidney, and must be transported Correspondence: A Poorabbas or F Fallah, Ilam Medical University, Ilam Ms 98, to other tissues. It is most concentrated in tissues that use Iran. fatty acids as their primary dietary fuel, such as skeletal and E-mail: [email protected] Received 15 September 2005; revised 2 November 2006; accepted 3 cardiac (heart) muscle (Arrigoni-Martelli and Caso, 2001). November 2006; published online 21 February 2007 Carnitine acyltransferases have crucial functions in fatty acid L-carnitine level in Type II diabetic women A Poorabbas et al 893 metabolism. Members of this enzyme family show distinctive pathy. Diagnosis of retinopathy was carried out by fundo- substrate preferences for short-, medium- or long-chain fatty scopic examination of the eye, neuropathy with acids. The molecular mechanism for this substrate selectivity is examination with current methods. All the patients were not clear because so far only the structure of carnitine screened for lipid profile. Serum total cholesterol, high- acetyltransferase has been determined (Gerwald et al., 2005). density lipoprotein (HDL), triglycerides (TG), low-density Carnitine deficiency may be primary or secondary. In all cases, lipoprotein (LDL) and glucose concentrations were measured secondary carnitine deficiencies are characterized by decreased using enzymatic methods. availability of free L-carnitine.Insuchcases,totalcarnitinelevels The sample was transported on dry ice to the laboratory may be normal, but free L-carnitine levels are decreased. where serum was separated from the cells. Serum was stored Factors such as sex, age, nutritional status, fasting and at À201C before batch analysis. Free L-carnitine concentra- disease have been cited as influencing plasma carnitine tion in serum was estimated by using the Boehringer- levels in man (Cederblad, 1987). Plasma carnitine levels have Manheim kit. This kit utilizes the enzymatic UV test been found to be normal or decreased in studies on carnitine described by Weiland (1985). metabolism in diabetes mellitus patients (Okuda et al., 1987; The results are presented as mean7standard deviation Winter et al., 1987; Pregnant et al., 1993). (s.d.). The cutoff level for statistical significance was set at Diabetes in animals and human lead to deterioration Po0/05. Unpaired Student’s t-test (two-tailed) and analysis of carnitine and lipid metabolism (Depalo et al., 1981; of variance (ANOVA) test were used to determine differences Cederblad et al., 1982; Hoppel and Genuth, 1982; Stearns, between independent groups. 1983; Brooks et al., 1985; Aoshima et al., 1993). It is well known that streptozotocin-induced diabetic rats develop myocardial carnitine deficiency (Vary and Neely, 1982; Results Brooks et al., 1985; Aoshima et al., 1993). In several studies, decreased carnitine concentrations in diabetic animals have According to the study results, increase in age was positively been observed (Vary and Neely, 1982; Aoshima et al., 1993). related with increasing BMI. Total dietary fiber consumption Acute hypercarnitinemia stimulates nonoxidative glucose was lower than normal levels (25 g/day). Table 1 shows the disposal during euglycemic hyperinsulinemic clamp in concentrations of serum glucose and plasma lipids profile. healthy volunteers. Similar results were obtained in type II Fasting blood glucose (FBG), TG, total cholesterol, LDL-c and diabetic patients (Cattolica et al., 2004). L-carnitine, which is VLDL-c levels were significantly higher in the case group required for mitochondrial free fatty acid (FFA) transport/ than in the control group (Table 2). oxidation, has been reported to improve vascular function in Study results indicated that the mean serum-free L- subjects with diabetes and heart disease (Shankar et al., carnitine concentration in the case group was significantly 2004). The above studies suggest a relationship between lower than its mean concentration (39.6378.99 vs diabetes and FFA and plasma carnitine. 53.4270.93 mmol/l, respectively, Po0.001 level) in the The aim of the present experimental study was to control group (Table 3). Free carnitine (FC) levels of the investigate the content of free L-carnitine in type 2 diabetic groups with hyperlipidemia, and polyneuropathy and women with and without complications. retinopathy were not significantly different when compared with each other (P40.05) (Table 3). Methods Table 1 Characteristics of anthropometrics, blood pressure, FBS and In the present case – control study, the levels of serum-free lipid profiles L-carnitine, blood glucose and lipids, systolic and diastolic Case Control P value blood pressure, body mass index (BMI) and nutritional factors participating in carnitine biosynthesis (iron, vitamins Age 54.4578.97 5278.71 0.350 Weight (kg) 73.7379.50 58.5672.59 0.001 B6, niacin and vitamin C) were determined in 33 diabetic o Height (m) 155.55 75.75 154.0675.13 0.363 women with complications (case group) and 18 diabetic BMI (kg/m2) 29.4774.32 23.6671.74 o0.001 women without complications (control group) of the same Systolic BP (mm Hg) 155.61728.61 13578.74 0.005 age (30–65 years), who were selected by the simple sampling Diastolic Bp (mm Hg) 91.8278.91 85.8377.91 0.021 method. FBS (mg/dl ) 212.48786.40 147.89723.06 0.003 Total-cholesterol (mg/dl ) 238.52757.12 135.06710.71 0.001 In this study, patients with CHD, anemia, chronic renal o LDL-c (mg/dl ) 160.03720.63 75.67718.63 o0.001 failure, heart failure, liver cirrhosis, antiepileptic drug users VLDL-c (mg/dl ) 48.5677.20 19.5074.82 o0.001 and those who receive carnitine treatment were excluded TG (mg/dl ) 298.307116.50 120.17722.59 o0.001 from the study. The patients were grouped into four groups, HDL-c (mg/dl ) 36.6778.34 39.6176.62 0.201 the control group included the patients with no complica- Abbreviations: BMI, body mass index; FBS, fasting blood sugar; HDL-c, high- tions and the case group was divided into three subgroups, density lipoprotein
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