Prevalence of Lp(a) in diabetes and normal population

 

V Hariharan¹, K P Mekhala^2*, Jyothsana³, S Ramya⁴

 

Abstract               Background: Lipoprotein a-Lp(a) has similar structure of LDL except it has one more Apo-A protein. It is produced in liver and it is highly atherogenic. Lp(a) is usually genetically predisposed but seemed to have associated with Diabetes in few studies. Aims: In this study we investigated the relationship between Lp(a) levels with incidence of Diabetes; relationship between glycemic control and Lp(a); relationship between Triglyceride/HDL ratio and Lp(a) levels. Materials and Methods: 119 Diabetics and 120 age matched non diabetics were taken for this study. Their HbA1c, Lp(a) levels, Triglyceride/HDL ratio were quantified and compared. Results and conclusion: No relation was found between the levels of Lp(a) among Diabetics and non diabetics. It was also seen that there is no significant correlation between glycemic control and Lp(a). Even TG/HDL ratio was not comparable with Lp(a) levels

Key Word: Lipoprotein a, Lp(a), Type 2 Diabetes, HbA1c

 

 

INTRODUCTION

Type 2 Diabetes patients have two to four-fold increased risk of Cardiovascular disease than non-diabetic population.¹The levels of cardiac risk markers like High density lipoprotein (HDL) is reduced in Diabetes; and Triglycerides and Low density Lipoproteins are increased when compared to healthy subjects. Even though these can explain the increased risk of CVD in Diabetics, they provide only partial explanation of the increased risk.² When searching for further clues in this subject it is evident that Lp(a) is a major risk factor for cardiovascular disease and is considered as important independent predictor of heart disease³. Berg and associates discovered Lipoprotein(a).⁴ Lp(a) consists of apolipoprotein A attached to apolipoprotein B-100 by disulphide linkages produced by the hepatocytes. The LDL-like moiety is composed of a central core of cholesteryl esters and triglycerides surrounded by phospholipids, free cholesterol and a single molecule of apoB. Lp(a) even though differs from LDL in structure, its physical and chemical properties are similar to that of LDL. But when drugs and dietary measures used to reduce LDL levels does not seem to affect Lp(a) levels.⁵ Numerous studies have investigated the role of Lp(a) and CVD risk in general populations. A meta-analysis of 126,634 participants from 36 prospective studies, demonstrated that plasma Lp(a) level is continuously associated with an increased risk of CVD and stroke⁶. Lp (a) is structurally similar to plasminogen and tissue plasminogen activator, and it can increase thrombogenesis and can inhibit fibrinolysis. Lp (a) is a preferential carrier of oxidized phospholipids, which attracts inflammatory cells to arterial vessel wall and leads to smooth muscle proliferation. Many studies tried to find out the association of Lp(a) in diabetes, but none found a significance. Arauz et al.⁷ found a higher mean concentration of Lp(a) in a combined group of type 1 and type 2 diabetic subjects but found no association of glycated hemoglobin with Lp(a) in type 2 subjects. In one study of well controlled type 2 diabetics, the Lp(a) concentration was actually lower in diabetics than in the non-diabetic control subjects.⁸ Chico et al.⁹ found no difference in the mean Lp(a) concentration between diabetic and non-diabetic subjects. The possible association of the Lp(a) levels and the metabolic control is of major interest since the serum concentration of apoprotien(a), the unique protein of Lp(a), may be genetically controlled to a large degree.². TG/HDL ratio is a marker of poor metabolic control. The present study aimed to evaluate the association of the Lp(a) levels with type 2 diabetes mellitus versus non diabetic population. Also its association with the degree of glycemic control and Triglyceride/HDL ratio are secondary objectives.

 

METHOLOGY

This is a cross sectional observational study done among patients attending in Karpagam Medical College Hospital OPD, Coimbatore, India. 119 age matched Type 2 Diabetics and 120 age matched non diabetics were taken for the study. Only known diabetics of 5 year history between ages of 35-55 years only on oral hypoglycemic drugs with Hba1c >6.4 were taken as cases. Controls were the people without history of Diabetes and HbA1c less than 6. Known coronary artery disease patients and patients on dyslipidemic drugs were excluded from the study. After obtaining Institutional Human Ethical committee clearance, study was started and conducted between june-July 2017. After obtaining Informed consent, 3 ml of Blood was collected and immediately was taken up for centrifugation and analysis. Hba1c was measured using Ion exchange resin chromatography method, Lp (a) was measured using immuno nephelometry, Triglycerides and HDL will be measured and analyzed using routine methods. After analysis, correlation between HbA1c and Lp(a), correlation between Lp(a) and TG/HDL ratio were done using independent T test using SPSS 16 software. p<0.05 were considered significant.

 

RESULTS

Characteristics of the study subjects: The average age of non Diabetic controls was 42years whereas it was 47 years for the Diabetic cases. Totally 45 females and 74 males were taken as cases and 52 females and 68 males were taken as controls. The average duration of Diabetes among controls was 8.5 years. Hba1c of cases Varied from 6.4 to 11.3, with mean of 8.25. The Triglyceride/HDL ratio mean for Diabetic cases was 4.82 which is very high. For Non Diabetics the TG/HDL ratio was 2.5. We did not find any significant relationship on Lp(a) levels in Diabetics an non Diabetics as seen in Table 1.

 

Table 1: Relationship between Lp(a) levels in Diabteics and non Diabetic population.

Also we did not find any significance in Lp(a) levels among diabetics on varied HbA1c levels as seen in Table 2.

Table 2: Relationship between Lp(a) levels and Hba1c levels

No significant relationship found between Lp(a) levels and Triglyceride/HDL ratio in Diabetic population. This is shown in Table 3.

 

Table 3: Relationship between Lp(a) levels and TG/HDL ratio in Diabetic population

 

DISCUSSION

Lp(a) plasma concentrations are genetically determined. It is controlled by the Apolipoprotein A gene located in chromosome 6. There are various Apo (a) isoforms. There seems a general inverse correlation between size of Apo(a) isoform and plasma Lp(a) levels¹⁰. The levels of Lp(a) in population varies widely from 2-200 mg/dL. Higher levels are strongly associated with cardiovascular disease(CVD) and there is no treatment available to treat high Lp(a). Age and sex does not seems to be related to Lp(a) levels. The current study aimed to find any relation between Diabetes and Lp(a) because it is well known that Diabetes is the most important factor for Heart disease. Mora et al in 2010 carried a study on 26,746 women showed a higher level of Lp(a) in Diabetics on which the current study is based. But from this study we can observe that there seems to be no relation between Diabetes and Lp(a) as well as glycemic control and Lp(a). May be Lp(a) is purely genetically determined. Only glycemic control in Diabetics and control of dyslipidemia cannot confer protection from high Lp(a) as seen in the current study. European atherosclerosis Society recommends Lp(a) levels screening for patients with moderate to high risk of CVD such as premature CVD, Familial Hypercholesterolemia, Family history of CVD, Family history of elevated Lp(a), recurrent CVD¹². Even high dose Atorvastatin proved inefficient in lowering Lp(a) levels¹³. Niacin on larger doses can reduce Lp(a) up to a meagre 30% but on small doses seemed useless¹⁴. We have to keep in mind that Niacin on larger doses may produce side effects on many. Low doses of aspirin showed 20% reduction in Lp(a) among Japanese population¹⁵. We have a poor knowledge on structure and function of Lp(a), its pathophysiology on causing atherosclerosis, clear incidence and associations with other diseases. Also there is no proven protocol in place to reduce Lp(a) levels. Future research must target on these lines.

 

CONCLUSION

This study re affirms that there is no relationship between Diabetes or glycemic control versus Lp(a) levels. Large trials must be made on the prevalence of High Lp(a) among Indians and animal and human studies must be done to find out treatments for high Lp(a).

 

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