Extended lipid profile and urine albumin-creatinine ratio in type 2 diabetes mellitus

Background : Diabetes is a chronic metabolic disorder and has become the one of the most challenging global health problem of 21 st centuary. Diabetic nephropathy is a major complication of diabetes and an established risk factor for cardiovascular events. Lipid abnormalities occur in patients with diabetic nephropathy, which further increase their risk for cardiovascular events. We aimed to research association between extended lipid profile and urine albumin-creatinine ratio (UACR), hypothesizing that early detection and treatment of lipid abnormalities can minimize the risk for atherogenic cardiovascular disorder and cerebrovascular accident in patients with type 2 diabetes mellitus. Methods : A hospital based cross-sectional study was conducted on 48 patients with type 2 diabetes mellitus. All patients fasting blood glucose (FBG), HbA1c, total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG), apolipoprotein-A (apo-A), apolipoprotein-B (apo-B), lipoprotein (a){Lp(a)} and urine-albumin creatinine ratio (UACR) evaluated. Patients taking steroids, any renal disease other than diabetic nephropathy and patients of uncontrolled hypertension were excluded from study. Based on UACR level patients were divided into three sub groups: normal ( < 30 mg/g), microalbumiuria (30-300 mg/g) and macroalbuminuria ( > 30 mg/g). Comparison between three subgroups of UACR and extended lipid profile was made using non parametric test (Kruskal Willis Test). Fisher’s exact test was used to explore the association between UACR and extended lipid profile. Result : 20.8% patients had UACR < 30 mg/g, 54.2% patients had UACR:30-300 mg/g, 25.0% patients had UACR: ≥ 300 mg/g; 62.5% patients had Lipoprotein(a): < 30 mg/dl and 37.5% patients had Lipoprotein(a): > 30 mg/g. Significant association was found between UACR and Lipoprotein(a):  100


Introduction
Diabetes Mellitus is one of the most challenging health problem of 21 st century and has become global health problem now. The global diabetes prevalence in 2019 is estimated to be 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. The prevalence is higher in urban (10.8%) than rural (7.2%) areas, and in high-income (10.4%) than low-income countries (4.0%) (1). Overall prevalence of Diabetes in India is 8.7% in the age group of 20 and 70 years (2).
Plasma lipid and lipoprotein abnormalities in diabetes, includes a significantly higher concentration of total cholesterol, triglycerides and low density lipoprotein (LDL) cholesterol and apolipoprotein-B (Apo-B), but a lower concentration of high density lipoprotein (HDL) cholesterol and apolipoprotein-A (Apo-A) (3). Progressive diabetic renal disease occurs in 20-40% of patients with diabetes and is the leading cause of end stage renal disease. Persistent increased albuminuria in the range of UACR 30-299 mg/g is an early indicator of diabetic kidney disease and is a marker for development of progressive diabetic kidney disease in type 2 diabetes. Diabetic dyslipidemia is characterised by elevated fasting and post prandial triglycerides (TGL), low HDL-cholesterol, elevated LDL-cholesterol with predominance of lipoprotein (a).
Dyslipidemia concurrently with persistent increased albuminuria is considered as an alarming signal for both atherosclerotic cardiovascular disease (ASCVD) and end stage renal disease (ESRD). Detection of dyslipidemia with a corresponding increased UACR in the early setting of diabetes mellitus and its therapeutic intervention could control the resulting cardiovascular and renal complications (4,5). In this study we evaluate the individual fractions of Extended lipid profile and UACR in subjects with Type-2 Diabetes mellitus and try to find out any association between Extended lipid profile and UACR in patients of type2 DM.

Material and methods
Hospital based Cross Sectional study was conducted at a tertiary care hospital in India after obtaining necessary ethical clearance. After taking proper informed consent, 48 adult patients, aged18 years or older with T2DM were taken as study subject. Subjects with uncontrolled hypertension, taking steroids, urinary tract infection, hematuria, thyroid dysfunction and any renal disease other than diabetic nephropathy were excluded from study. CBC, LFT, KFT, fasting BS, 2 hours PPBS, HbA1c, URM, UACR, Lipid profile and Extended lipid profile was done. Extended lipid profile was done by ELISA based kits and reader. UACR was done in Beckman coulter AU 680 Machine using urine albumin and urine creatinine insert method. [Urine Albumin (mg/dl) / Urine Creatinine (g/dl) = UACR in mg/g = Albumin excretion in mg/day].Study subjects were divided according to UACR as normal (<30mg/g), microalbuminuria (30-300mg/g) and macroalbuminuria (>300mg/g).

Statistical analysis
The observations were compiled, tabulated and analysed statistically using MS EXCEL spreadsheet and SPSS. Continuous data was presented as mean and standard deviation. Proportion of deranged Extended lipid profile and UACR was calculated. Comparison between three subgroups of UACR and Extended lipid profile was made using non parametric test (Kruskal Willis Test). Fisher's exact test was used to explore the association between UACR and Extended lipid profile.
There was a significant difference between the various groups of UACR in terms of distribution of Lipoprotein-a (χ2 = 8.479, p = 0.010) was found with strength of association between the two variables (Bias Corrected Cramer's V) = 0.37 (Moderate Association).

Figure 1 Association between UACR and Lipoprotein-a
There was no significant association was found between various groups of UACR with Apo-A and Apo-B was found among Extended lipid profile.

Discussion
In

Glycemic control of patients
In present study 8.5% (4) of patients had HbA1c level ≤7 % and 91.5% (43) patients had HbA1c level >7%. It was observed that patient having uncontrolled blood glucose with HbA1c >7% are associated with more prevalence of albuminuria, the same was also observed in a study conducted by Sana M, Chaudhry M, Malik A, et al. [7]

Diabetic nephropathy and UACR of patients
Chronic kidney disease (CKD) in patients with type 2 diabetes is associated with increased risk of end-stage renal disease (ESRD) and cardiovascular disease (CVD). Urine albumin-to-creatinine ratio (UACR) is a sensitive and early indicator of progressive diabetic kidney damage, which should be used routinely to accurately assess CKD stage and to monitor kidney damage.
In a study conducted by Sana M, Chaudhry M, Malik A, et al. on prevalence of microalbuminuria in type 2 DM it was found that the mean age of the participants was 54.5 ± 10.3 years which included 60.9% males and 39.1% females. The overall incidence of diabetic nephropathy was 30.1%, with 25.6% having microalbuminuria and 4.5% having macroalbuminuria (7).

Extended lipid profile of patients
In our study evaluation of extended lipid profile results showed that the mean (SD) of Apo-A (mg/dl) was 96.08 (33.91); the mean (SD) of Apo-B (mg/dl) was 74.52 (31.00) and the mean (SD) of Lipoprotein(a) (mg/dl) was 42.61 (51.14) respectively; with 70.8% of the participants had Apo-A: <110 mg/dl; 29.2% of the participants had Apo-A: ≥110 mg/dl; 68.8% of the participants had Apo-B: <80 mg/dl, 31.2% of the participants had Apo-B: ≥80 mg/dl; 62.5% of the participants had Lipoprotein-a: <30 mg/dl, 37.5% of the participants had Lipoprotein-a: ≥30 mg/dl.
In Indian context no any study was conducted in the past on each component of Extended lipid profile {Apo-A, Apo-B, Lp(a)}.

Association between extended lipid profile and UACR
A significant association between the patients with various subgroups of UACR in terms of distribution of Lipoproteina (χ2 = 8.479, p = 0.010) was found in our present study with the strength of association between the two variables (Bias Corrected Cramer's V) = 0.37 (Moderate Association  Participants with UACR: <30 mg/g had the largest proportion of participants with Lipoprotein (a): <30 mg/dl.  Participants with UACR: >300 mg/g had the largest proportion of participants with Lipoprotein (a): ≥30 mg/dl. There was no significant association between the patients with various subgroups of UACR in terms of distribution of Apo-A was found (χ2 = 2.253, p = 0.362) with the strength of association between the two variables (Cramer's V) = 0.22 (Low Association). Similarly there was no significant association between the patients with various subgroups of UACR in terms of distribution of Apo-B (χ2 = 0.577, p = 0.840) was found with the strength of association between the two variables was (Cramer's V) = 0.11 (Low Association) No any such study was conducted in past on association between Extended lipid profile and UACR.
In our study mean(SD) value of the of total cholesterol (mg/dl) was 159.96 (53.11) with most of study subject(89.6%) had total cholesterol <200 mg/dl and rest of the study subjects had total cholesterol >200 mg/dl; the mean(SD) of triglycerides (mg/dl) was found to be 146.81(64.10) with most of the study subjects (64.6%) have triglyceride <150mg/dl and 35.4% of study subjects had triglycerides level >150 mg/dl; the mean(SD) of HDL was 38.08 (12.54) mg/dl with 62.5% of participants had HDL <40 mg/dl and rest of the participants had HDL >40 mg/dl and the mean (SD) of LDL (mg/dl) was 101. This difference in lipid profile can be due to smaller sample size, geographical and demographical variation in the study population, and not taking into account other confounders such as hypothyroidism, liver disease, use of drugs or toxins (alcohol, herbal preparation, etc) which can alter lipid profile.
Many previous study showed that increased lipoprotein (a) [Lp(a)] concentrations are predictive of atherosclerotic cardiovascular disease (ASCVD). In our current study significant positive association found between increased Lp(a) and UACR was found. Since Lp(a) investigation is not widely available, accessible and had varied estimation technique hence UACR can be used as a surrogate marker of risk for ASCVD.

Conclusion
 Microalbuminuria were present in most of the patients which is an early indicator of progressive diabetic kidney disease.  Albuminuria measured in the form of raised UACR had statistically significant association with increased Lipoprotein (a) level and consequently there is increased risk of atherosclerotic cardiovascular disease (ASCVD) as proved in many independent studies.  Since lipoprotein (a) investigation is not widely available, accessible and has varied estimation techniques hence UACR can be used as a surrogate marker for raised lipoprotein (a) and an increased risk of ASCVD.