HDL/LDL ratio as risk factor in type 2 DM
9
HDL/LDL RATIO AS A RISK FACTOR IN TYPE 2 DIABETES MELLITUS
Gowtham K1, Gandhe MB2*, Salwe KJ3, Srinivasan AR2
1. Second year MBBS, Mahatma Gandhi Medical College and Research Institute, Sri
Balaji Vidyapeeth [SBV] University, Pillaiyarkuppam, Puducherry-607402, India
2. Department of Biochemistry, Mahatma Gandhi Medical College and Research
Institute, Sri Balaji Vidyapeeth [SBV] University, Pillaiyarkuppam, Puducherry-607402,
India
3. Department of Pharmacology, Mahatma Gandhi Medical College and Research
Institute, Sri Balaji Vidyapeeth [SBV] University, Pillaiyarkuppam, Puducherry-607402,
India
Correspondence
Dr. Mahendra Gandhe. Department of Biochemistry, Mahatma Gandhi Medical College
and Research Institute, Sri Balaji Vidyapeeth [SBV] University, Pillaiyarkuppam,
Puducherry-607402, India.
Email: [email protected]
Gowtham K, Gandhe MB, Salwe KJ, Srinivasan AR. HDL/LDL ratio as a risk factor in
type 2 diabetes mellitus. Adv Lab Med Int. 2012; 2(1): 9 - 18.
Supporting funding: This project was funded and supported by Indian Council of Medical
Research (ICMR)
ABSTRACT
Diabetes mellitus (DM) is characterized by hyperglycemia, due to deficiency or
diminished effectiveness of insulin. Patients with Type 2 Diabetes mellitus are at an
increased risk for cardiovascular morbidity and mortality. The present study was
designed to investigate the HDL/LDL ratio and their correlation with other biochemical
parameters like fasting blood sugar (FBS), HbA1c (glycated hemoglobin) and
triacylglycerol (TAG) in Type 2 Diabetes mellitus subjects, since no significant
correlation could be established between Lp(a) and LDL: HDL ratio. Here, the
lipoprotein (a) is not considered as an indicator, instead HDL/LDL ratio is taken as the
indicator for cardiovascular diseases in type 2 diabetic patients. Moreover, HDL/LDL
ratio is an economically viable alternative to Lp(a) estimation. The study included 30
male cases (Diabetic group) and 30 controls (Non Diabetic group). Diabetes mellitus was
diagnosed according to American Diabetes Association (ADA) criteria 2000 (Fasting
glucose level ≥126mg/dl and 2-hour postprandial ≥200mg/dl). In the present study, we
quantified HDL and LDL cholesterol levels and correlated HDL/LDL ratio with HbA1c
levels and fasting blood glucose. The levels of the fasting blood glucose and HbA1c were
found to be significantly increased in the Diabetic group as compared to the control
group. The typical pattern of dyslipidaemia seen in type 2 Diabetes is normal or slightly
elevated total cholesterol, elevated triacylglycerol and low levels of high density
lipoprotein (HDL)-cholesterol levels. Low density lipoprotein (LDL)-cholesterol levels
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HDL/LDL ratio as risk factor in type 2 DM
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are variably elevated, but not significantly different from non-diabetic patients. From the
present study, we can conclude that Type 2 Diabetes mellitus is strongly associated with
increased levels of Low density Lipoprotein cholesterol invariably in some cases but
statistically not significant LDL alteration and decreased level of High density
Lipoprotein cholesterol due to which there is significantly low HDL: LDL ratio in
diabetic group as compared with the control group. Also, there is significant correlation
between glycated hemoglobin (HbA1c) and HDL: LDL ratio. The HDL/LDL ratio is the
most appropriate related predictor of future cardiovascular events in Type 2 Diabetes
mellitus.
Key words: HDL/LDL ratio, Type 2 Diabetes mellitus, Obesity, glycated hemoglobin
INTRODUCTION
Diabetes mellitus (DM) which is referred to as the ‗iceberg disease‘ is the most common
endocrine disorder.1 It is characterized by hyperglycemia, due to deficiency or
diminished effectiveness of insulin. According to the World Health Organization (WHO)
estimates, India had 32 million diabetic subjects in the year 2000 and this number
would increase to 80 million by the year 2030.2 The International Diabetes Federation
(IDF) also reported that the total number of diabetic subjects in India is 41 million in
2006 and that this would rise to 70 million by the year 2025.3 India leads the world
with largest number of diabetic subjects earning the dubious distinction of being
termed the ―diabetes capital of the world‖. Among the two types of diabetes, the most
common one is the type 2 diabetes mellitus. The type 2 Diabetes mellitus which was
known earlier as Non-Insulin Dependent Diabetes Mellitus (NIDDM), accounts for about
85% to 95% of all the diabetes among different populations of the world.4
Type 2 Diabetes mellitus (DM) is one of the most serious public health problems, faced
by both developed and developing countries. India is one among those seriously affected
country. Type 2 Diabetes mellitus is a multifactorial complex disease, which includes
sedentary life style, dietary habits and the major genetic factors. Diabetic individuals are
quite vulnerable to many long term complications. Of all the long term complications,
cardiovascular disorder is the most serious outcome in terms of morbidity & mortality.
The incidence of type 2 diabetes mellitus is increasing worldwide mostly due to
increasing prevalence of obesity and a longer life expectancy.5,6 Since type 2 diabetic
patients are resistant to insulin, they are at an increased risk of developing metabolic
syndrome, a major cause of cardiac failure and dyslipidaemia.7
The risk of cardiovascular disease in type 2 diabetic subjects is increased three to four
folds over age matched non diabetic subjects.8 Clinically, the overall mortality from
coronary heart disease (CHD) is two to three times high in diabetic subjects compared to
non-diabetic group.8 Hypertension and longer duration of diabetes were correlated with
increased risk of developing vascular complication. Dyslipidemia is an important feature
of type 2 diabetes; and contributes significantly to the greater CHD risk.9 Considerable
data has suggested that besides total cholesterol (Tc), elevated triacylglycerol (TAG)
concentrations, increased LDL-cholesterol and decreased HDL cholesterol contribute to
cardiovascular diseases.10 LDL particle size and density also has a significant role in lipid
abnormalities. Supportive clinical evidence shows that, the risk of CHD in type 2
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HDL/LDL ratio as risk factor in type 2 DM
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diabetics is prevented by giving hypolipidaemic drugs like statins as a precautionary
measure.11 Hyperinsulinemia associated with hypertension and low HDL cholesterol
enhances coronary heart disease.
HDL which is also known as the ―good cholesterol‖ and LDL which is also known as the
―bad cholesterol‖ should be in appropriate levels to protect from any coronary vascular
disease. The normal HDL/LDL ratio should be around 0.3 and above, to stay away from
any cardiovascular disorders. In case, the value is reduced considerably, then the
individual is susceptible more to acquire any cardiovascular disorders in type 2 diabetic
individuals.
There are very few studies in southern part of India implicating HDL/LDL ratio as a risk
factor in type 2 Diabetes Mellitus. So, the present study was planned to show HDL/LDL
ratio as a direct indicator, for suspecting a type 2 diabetic individual to get any
cardiovascular complication. To support the above condition, a comparative analysis with
different biochemical parameters is done.
Since Type 2 diabetics are more prone to get cardio vascular disorders, aim and
objectives of research are:
1. To assess the link between HDL/LDL ratio and glycemic control.
2. To estimate fasting blood glucose (FBS) & HbA1c levels.
3. To quantify HDL and LDL cholesterol and compute HDL/LDL ratio.
4. To find out whether HDL/LDL ratio correlates with HbA1c levels and could be used
as an indicator of glycemic control in light of cardiovascular complication.
MATERIALS AND METHODS
A.
General
A case-control study was conducted in Tertiary care hospital. This study was carried
around a semi-urban population. The study included 30 cases (Diabetic group) and 30
controls (Non Diabetic group). The subjects included 30 male patients with type 2
diabetes mellitus. Diabetes mellitus was diagnosed according to American Diabetes
Association (ADA) criteria 2000. (Fasting glucose level ≥126mg/dl and 2-hour post
prandial ≥200mg/dl). The subjects who did not meet ADA criteria, but were under
treatment with oral hypoglycemic agents or insulin were also considered to be diabetic.
Inclusion Criteria: Male Aged between 40-60 years, Type 2 diabetes mellitus
Exclusion Criteria: Type 1 diabetic patient, patient with history of angina, ketoacidosis,
myocardial infarction abnormal thyroid and liver function tests and patients with other
endocrine metabolic disorder as well as those with micro or macro vascular
complications were excluded from the study.
The control group comprised of 30 healthy age and sex matched subjects.
The subject‘s blood sample was collected by trained professionals under sterile
conditions and the sample was tested for various biochemical parameters like Fasting
blood glucose (FBS), glycated hemoglobin (HbA1c), HDL-cholesterol, LDL-cholesterol
and triacylglycerol (TAG).
Fasting Blood Sugar was measured by Glucose oxidase - Peroxidase (GOD-POD) assay
and expressed in mg/dl. Glycated Haemoglobin (HbA1c) was measured by Turbidimetric
inhibition immunoassay and expressed in percentage (%). Total cholesterol (Tc) was
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HDL/LDL ratio as risk factor in type 2 DM
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calculated based on enzymatic method and expressed in mg/dl. High Density
Lipoprotein (HDL) cholesterol would be calculated using polyanion precipitation and
expressed as mg/dl. Low Density Lipoprotein (LDL) cholesterol was calculated using
Friedewald‘s equation and expressed in mg/dl. Triacylglycerol (TAG) in serum was
converted to glycerol and then estimated using glycerol kinase enzyme based kinetic
method and expressed in mg/dl.
B.
Ethical clearance
Protocol was duly submitted to Institutional Human ethics committee and approval was
taken before starting the study. All the procedure was informed to the patient in his native
language and informed written consent was taken from them.
C.
Statistical analysis
Statistical analysis was done on Statistical Package for Social Sciences (SPSS, Chicago,
Version 12). Unpaired student‘s t test was done the control group is compared with the
diabetic group. Data were expressed as mean ± Standard deviation. The results were
rationally analysed. P < 0.05 was considered statistically significant.
RESULTS
There were 30 males in the diabetic group and 30 males in the control groups.
Fasting blood sugar was found significantly increased in the Diabetic group as compared
to the control group. (Table 1, Figure 2).
Table 1. Fasting blood Sugar (FBS), HbA1c, triacylglycerol (TAG) levels, and
HDL:LDL ratio in Diabetic and control group.
Parameters
Groups
Diabetics
Control
Diabetics
HbA1c (%)
Control
Diabetics
Triacylglycerol
(mg/dl)
Control
Diabetics
HDL/LDL
Control
*Significant level with p<0.05
** Highly Significant level with p<0.01
Fasting blood sugar
(mg/dl)
Mean ±
Standard Deviation
167.77 ± 63.696
84.33 ±10.937
8.0800 ±1.2343
5.0100 ±.7809
145.67 ±62.738
146.67 ±80.134
0.3101 ±0.09782
0.5748 ±0.5700
t –test
(58 d.f.)
P value
7.071
0.000**
11.512
0.000**
0.054
0.957
2.507
0.015*
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HDL/LDL ratio as risk factor in type 2 DM
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mg/dl
167.77
180
160
140
120
100
80
60
40
20
0
Control
84.33
Diabetics
Fasting blood sugar (FBS)
Figure 1. Comparison of fasting blood sugar (FBS) levels in control and diabetic groups.
Percentage
The level of the HbA1c was found significantly increased in the Diabetic group as
compared to the control group. (Table 1, Figure 2).
Figure
9
8
7
6
5
4
3
2:
2
1
0
8.08
5.01
Control
Diabetics
Comparison of HbA1c levels in control and diabetic groups
HbA1c
Figure 2. Comparison of HbA1c levels in control and diabetic groups.
There was no significant difference between the levels of the triacylglycerols (TAG) in
control and diabetic group. The levels were found to be almost similar in both the groups.
(Table 1, Figure 3)
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HDL/LDL ratio as risk factor in type 2 DM
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Figure 3. Comparison of Triacylglycerol (TAG) levels in control and diabetic groups.
HDL cholesterol levels were low in the diabetic group when compared with the control.
Similarly LDL cholesterol levels were significantly increased in the diabetic group when
compared to the control group. The HDL: LDL ratio was significantly lower in the
diabetic group as compared with the control group. (Table 1, Figure 4)
Figure 4. Comparison of HDL/LDL ratio in control and diabetic groups.
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HDL/LDL ratio as risk factor in type 2 DM
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DISCUSSION
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia, glycosuria,
hyperlipaemia, negative nitrogen balance and sometimes ketonaemia. A widespread
pathological change is thickening of capillary basement membrane, increase in vessel
wall matrix and cellular proliferation resulting in vascular complication like lumen
narrowing, early atherosclerosis.20
Cardiovascular disease is a major cause of both morbidity and mortality for patients with
type II diabetes mellitus occurring two to four times more frequently in the general
population.12
The present study was designed to investigate the HDL/LDL ratio and their correlation
with other biochemical parameters like fasting blood sugar (FBS), HbA1c and
triacylglycerol (TAG) in type 2 diabetes mellitus subjects, since no significant correlation
could be established between Lp(a) and LDL: HDL ratio.18 Here, the lipoprotein (a) is not
considered as an indicator, instead HDL/LDL ratio is taken as the indicator for
cardiovascular diseases in type 2 diabetic patients. Moreover, HDL/LDL ratio is an
economically viable alternative to Lp(a) estimation.
In our study it was found that the level of fasting blood sugar was significantly increased
in the diabetic group as compared to the control group. Glucose is the primary source of
energy for the body's cells, and blood lipids (in the form of fats and oils) are primarily a
compact energy store. Glucose is transported from the intestines or liver to body cells via
the bloodstream, and is made available for cell absorption via the hormone insulin,
produced by the body primarily in the pancreas. The mean normal blood glucose level in
humans is about 72 mg/dL (milligrams/deciliter); however, this level fluctuates
throughout the day. Glucose levels are usually lowest in the morning, before the first
meal of the day (termed "the fasting level").
Blood sugar levels outside the normal range may be an indicator of a medical condition.
A persistently high level is referred to as hyperglycemia; low levels are referred to as
hypoglycemia. Diabetes mellitus is characterized by persistent hyperglycemia from any
of several causes, and is the most prominent disease related to failure of blood sugar
regulation.
The level of HbA1c also increased significantly in diabetic group when compared to
control group. Glycated hemoglobin HbA1c is a form of hemoglobin which is measured
primarily to identify the average plasma glucose concentration over prolonged periods of
time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to
plasma glucose. Normal levels of glucose produce a normal amount of glycated
hemoglobin. As the average amount of plasma glucose increases, the fraction of glycated
hemoglobin increases in a predictable way. This serves as a marker for average blood
glucose levels over the previous months prior to the measurement. The 2010 American
Diabetes Association Standards of Medical Care in Diabetes suggested that HbA1c ≥
48 mmol/mol (≥6.5%) as another criteria for the diagnosis of diabetes.3 In Diabetes
mellitus higher amounts of glycated hemoglobin indicating poorer control of blood
glucose levels, have been associated with cardiovascular disease, nephropathy and
retinopathy. Monitoring the HbA1c in Type 2 Diabetes mellitus patients may thus
improve treatment.
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HDL/LDL ratio as risk factor in type 2 DM
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In our study there was no significant difference between the levels of the triacylglycerol
in cases and controls. In the human body, high levels of triacylglycerol in the
bloodstream have been linked to atherosclerosis (hardening of the arteries) and, by
extension, the risk of heart disease and stroke. However, the relative negative impact of
raised levels of triacylglycerol compared to that of LDL: HDL ratios is as yet unknown.
The risk can be partly accounted for by a strong inverse relationship between
triacylglycerol level and HDL-cholesterol level.13
The HDL: LDL ratio in the diabetic group was significantly decreased when compared to
the control group. This was due to decreased levels of the high density lipoprotein.
The typical pattern of dyslipidaemia seen in type 2 Diabetes is normal or slightly
elevated total cholesterol, elevated triacylglycerol and low levels of high density
lipoprotein (HDL)-cholesterol levels. Low density lipoprotein (LDL)-cholesterol levels
are variably elevated, but not significantly different from non-diabetic patients. Despite
similar LDL levels, type 2 diabetic mellitus patients have a more atherogenic LDL
phenotype than non-diabetic individuals. Diabetic patients have a shift to smaller, denser
LDL particles (phenotype B).14,15
Abnormal lipoprotein metabolism may account for the increased frequency of the
atherosclerotic lesion in diabetes. Many studies showed increased incidence of Coronary
arterial disease with low HDL and high Lp(a) below 40 years of age.16
Type 2 Diabetes mellitus is commonly associated with an abnormal lipoprotein
phenotype which is characterized by increased triacylglycerol, decreased HDL and an
accumulation of small dense LDL particles (the so called atherogenic dyslipidaemia
phenotype). A number of lipid related parameters have been used to predict the risk of
coronary artery disease (CAD). According to Grover, either the ratio of LDL/HDL or
TAG/HDL is the best related predictor of future cardiovascular events.17
Thus the results of our study clearly indicate that there is strong association between the
levels of HbA1c and HDL: LDL ratio. The levels of the Hb1Ac were found significantly
higher in the diabetic group. Similarly the ratio of HDL: LDL was also altered due to the
low levels of the protective high density lipoproteins. The results are similar to the
previous studies done by Seema single and Indumati V, though they have taken
LDL:HDL as the parameter because in their study the ratio was increased.18,19
Patients with type 2 diabetes mellitus are at an increased risk of cardiovascular morbidity
and mortality. The significant increase in Fasting blood sugar, Hb1Ac and alterations in
protective HDL and bad LDL of diabetic patients when compared to the control predicts
that patients with type 2 Diabetes mellitus are at a higher risk level for CHD.
CONCLUSION
From the present study we can conclude that type 2 diabetes mellitus is strongly
associated with increased levels of Low density Lipoprotein cholesterol and decreased
level of High density Lipoprotein cholesterol due to which there is alteration in the HDL:
LDL ratio. Also there is significant correlation between glycated hemoglobin (HbA1c)
and HDL: LDL ratio. No significant correlation could be established between
triacylglycerol and HDL: LDL ratio.
However there are some limitations of our study such as it was conducted in particular
area and sample size was also small.
Advance Laboratory Medicine International 2012; 2(1): 9 - 18.
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HDL/LDL ratio as risk factor in type 2 DM
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Hence for a better understanding a detailed prospective clinical study has to be instituted
in this direction to augment our claim.
ACKNOWLEDGEMENT
This project was funded and supported by Indian Council of Medical Research (ICMR).
CONFLICT OF INTEREST
No
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