Association of High Density Lipoprotein Cholesterol with Renal Function in Type 2 Diabetic Subjects in a Bangladeshi Population

Background: Abnormalities in lipid metabolism are associated with renal diseases. Association of serum lipid parameters with renal function is less studied in subjects with type 2 diabetes in Bangladeshi population. Objective: To assess the correlation of high density lipoprotein cholesterol with glomerular filtration rate (GFR) in type 2 diabetic subjects. Materials and Methods: One thousand three hundred thirty confirmed diabetic subjects advised for HbA1c, serum creatinine, serum total cholesterol, serum triglycerides, serum HDL cholesterol and LDL cholesterol were included in the study. Serum total cholesterol, HDL cholesterol, triglyceride, serum creatinine, HbA1c were measured by standard methods and serum LDL cholesterol was calculated by Friedewald’s formula. GFR was calculated by MDRD4 variables prediction equation. Total subjects were grouped according to sex; both males and females were subdivided into three subgroups depending on GFR values. Results of lipid parameters were compared by one-way ANOVA among different groups and correlation of lipid parameters with GFR were expressed by Pearson r. Results: HDL cholesterol was significantly different among different GFR groups (p<0.05) and positively correlated with GFR (r = 0.1386, p<0.001) in males. Total cholesterol and LDL cholesterol showed feeble positive correlation with GFR (r = 0.0789, p<0.05 for total cholesterol and r = 0.0768, p<0.05 for LDL cholesterol), but are not significantly different among GFR groups (p>0.05) in males. Total cholesterol, HDL cholesterol, LDL cholesterol, non-HDL cholesterol and LDLC/HDL-C were significantly different among three different GFR groups (p<0.01) and only HDL cholesterol and LDL-C/HDL-C showed weak correlation with GFR (r = 0.0770, p<0.05 for HDL cholesterol and r = -0.0803, p<0.05 for LDL-C/HDL-C) in females. Conclusion: The study revealed that HDL cholesterol was significantly and positively correlated with glomerular filtration rate in both male and female diabetic subjects and assessment of lipid parameters might be a helpful tool to prevent or delay the progression of renal insufficiency.


Association of High Density Lipoprotein Cholesterol with Renal Function in Type 2 Diabetic Subjects in a Bangladeshi Population
6][7] Low plasma high-density lipoprotein (HDL) has been identified as an independent risk factor for progression of renal disease. 8,9Animal studies showed that consumption of lipid-rich diet exacerbates and correction of hyperlipidemia attenuates the severity of glomerulosclerosis and tubulointerstitial fibrosis 3,6,[10][11][12] and normalization of HDL metabolism without changing serum total cholesterol retards the progression of renal disease in 5/6 nephrectomized rats. 13Studies on animal models of hyperlipidemia including apo-lipoprotein E knockout (apo E-KO) mice and Otsuka Long Evans Tokushima Fatty (OLETF) rats have also suggested the association of hyperlipidemia with the development of early renal lesions. 14,15Moreover, HDL serves as a potent endogenous inhibitor of inflammation, platelet adhesion and LDL oxidation. 16ince type 2 diabetes is recognized as an inflammatory condition associated with insulin resistance 17 and abnormal endothelial vascular reactivity 18 , HDL particles may partly play role to prevent progression of renal injury.We conducted this study to evaluate the relationship of lipid parameters, particularly HDL cholesterol with GFR in type 2 diabetic subjects in a Bangladeshi population.

Materials and Methods
This cross sectional study was carried out in the Department of Clinical Biochemistry, Bangladesh Institute of Health Sciences, Dhaka during July 2010 to August 2010.One thousand three hundred thirty specimens of confirmed diabetic subjects, both males and females, advised for HbA 1c , serum creatinine, serum total cholesterol, serum triglycerides, serum HDL cholesterol and LDL cholesterol were included for the study.HbA 1c was measured by HPLC based automated analyzer D-10 TM (Bio-Rad, USA), serum creatinine was measured by modified Jaffe's method using Dimension RxL Max (Siemens Health Care Ltd.).Serum total cholesterol, serum triglyceride and serum HDL cholesterol concentrations were measured by kits manufactured by Siemens Health Care Ltd.using Dimension RxL Max automated analyzer.Serum LDL cholesterol was calculated by Friedewald's formula 19 and eGFR was calculated using the simplified MDRD4 equation. 20Subjects were grouped according to sex, both males and females were subdivided into three groups depending to eGFR (Group-I, eGFR < 60 mL/min/1.73m 2 for males, eGFR < 55 mL/min/1.73m 2 for females; Group-II, eGFR 60-89 mL/min/1.73m 2 for males, eGFR 55-85 mL/min/1.73m 2 for females and Group-III, eGFR > 89 mL/min/1.73m 2 for males, eGFR > 85 mL/min/1.73m 2 for females).Results are expressed as mean ± SD and correlation of lipid parameters with eGFR were done by Statsoft STATISTICA version 8 for windows in the total study subjects, in male and female subjects and compared by GraphPad Prism version 5.03 for windows.
Comparison of lipid parameters among the three predefined eGFR groups is shown in Table II.One way ANOVA showed that only HDL cholesterol was significantly different among three eGFR groups in male diabetic subjects (Fig 1A  II).
The correlation coefficient of age, HbA 1c and lipid parameters with GFR is presented in Table III.The correlation coefficients of total cholesterol, HDL cholesterol and LDL cholesterol are statistically signi-ficant with eGFR in male diabetic subjects and correlation coefficients of HDL cholesterol and LDL-C/HDL-C are statistically significant with eGFR in female diabetic subjects (Table III).The correlation coefficient of HDL cholesterol is statistically significant in the total study population, and also in male and female diabetic subjects.

Discussion
In this study on diabetic subjects we observed significant differences of all lipid parameters except non-HDL cholesterol between males and females.Serum creatinine and eGFR were also significantly different between males and females.So we analyzed the association of lipid parameters with eGFR in male and female diabetic subjects separately.
In male diabetic subjects only serum HDL cholesterol was significantly different among different eGFR groups and showed positive association with eGFR.In different studies lipid parameters revealed different association with GFR.Krikken et al 21 showed that an inverse weak association exists between HDL cholesterol and GFR in nondiabetic subjects without kidney disease and Lin et al 22 found no association between lipid parameters and eGFR in female diabetic subjects.Kim et al 23 and Lin et al 24 showed that total cholesterol, triglycerides, LDL cholesterol and non-HDL cholesterol were inversely associated with eGFR.Lin et al 24 also showed that serum HDL cholesterol was positively associated with eGFR in male diabetic subjects.Our results are partly consistent with the study of Lin et al 24 and we found that positive association of serum HDL cholesterol with GFR is stronger in males than in females.From our study we can conclude, though traditional lipid parameters are not sufficient to explore the association of lipid parameters with GFR 25 , still their measurement and assessment may be helpful to prevent the progression of renal insufficiency.
) and total cholesterol, HDL cholesterol (Fig 1B), LDL cholesterol, non-HDL cholesterol and LDL-C/HDL-C were significantly different among different eGFR groups in female diabetic subjects (Table

Table I :
Comparison of different variables between male and female diabetic subjects

Table II :
Comparison of lipid parameters among different GFR groups in male and female diabetic subjects