Key words: lipid profile, diabetes mellitus, hypertriglyceridaemia

Diabetes is a common endocrine disease and its complications are major stimuli for the enhancement of efforts towards its control. There are currently 119.2 million people with type 2 diabetes worldwide, and the number is expected to increase to 212.9 million, in the year 2011 (1).

Type 2 diabetes is the most prevalent form of diabetes and is due to the combination of insulin resistance and defective secretion of insulin by pancreatic b-cells (2).
Diabetes mellitus is a major risk factor for morbidity and mortality due to coronary heart disease (CHD), cerebrovascular disease, and peripheral vascular disease. Metabolic control and duration of type 2 diabetes are important predictors of coronary heart disease (ischaemic heart disease) in elderly subjects, particularly in women (3).
Hyperglycaemia affects biochemical parameters and influences the progression of coronary heart disease and mortality rates in diabetic patients. Aggressive treatment to control hyperglycaemia is much more effective in reducing the number of complications than standard treatment (4, 5).

The term hyperlipidaemia refers to an increase in concentration of one or more plasma or serum lipids, usually cholesterol and triglycerides and the term dyslipidaemia is used for either an increase or decrease in concentration of one or more plasma or serum lipids. Type 2 diabetic patients have markedly increased risk of coronary heart disease than similarly dyslipidaemic non-diabetic subjects (1).
Most recently, results of the Strong Heart Study indicate that LDL cholesterol is an independent predictor of cardiovascular disease in patients with diabetes, along with age, albuminuria, fibrinogen, HDL cholesterol (inverse predictor), and percent body fat (inverse predictor) (4). Atherogenic dyslipidaemia (diabetic dyslipidaemia) is characterized by 3 lipoprotein abnormalities: elevated very-low-density lipoproteins (VLDL), small LDL particles, and low high-density lipoprotein (HDL) cholesterol (the lipid triad) (5, 6). Despite the high and widespread prevalence of dyslipidaemia among people with and without diabetes, only 2.2 % (7) of adults without diabetes and 32 % (8) of diabetic patients were receiving treatment with diet, exercise, or drugs to reduce lipid levels and less than one third of patients with established cardiovascular disease received such treatment. (7). Furthermore, among those who were being treated, only 1 % reached the American Diabetes Association (ADA) goal of LDL < 2.6 mmol/L (100 mg/dl) (8).

The aims of the present study were:

1. To know the incidence of hypertriglyceridaemia, its age and sex distribution and prevalence in NIDDM and IDDM.
   
2. To know the relationship between the glycaemic control and degree of hypertriglyceridaemia and incidence of complications of hypertriglyceridaemia in diabetes mellitus.

The sample of this prospective study was conducted in the department of medicine in King Hussein medical center over a period of two years.

After institutional ethical committee clearance and written informed consent was taken, one hundred and twenty patients of well-established diabetes mellitus were included in the study.

Patients were selected for study from among patients attending the Outpatient Diabetes Clinic.

The selection criteria were:

1. Every patient of these one hundred and twenty cases had established diabetes mellitus.
   
2. Systemic diseases like CRF, nephrotic syndrome, myxoedema, SLE were excluded from the study on the basis of history, clinical examination and relevant investigations.
   
3. Diabetic patients taking drugs like beta-blockers, oral contraceptive pills, thiazide diuretics, corticosteroids, or cimetidine for any reason, were also excluded.
   
4. Smokers and alcoholics were also excluded.
   

Those patients who agreed to participate in the study were informed of the program and schedule of the study.

The patient's personal data, medical, family, dietary history and daily activities were recorded. Height and weight for BMI calculation were also measured and recorded using a data collection form.

After 12 hours of fasting (overnight) a sample of blood was collected into appropriate tubes and taken to Chemical Pathology Laboratory for analysis.

All patients underwent the following investigations:

1. Base line investigations like blood CP with ESR, Blood urea, urine RE, ECG and x-ray chest.
   
2. Planned investigations: These included fasting and 2 hours post prandial blood glucose estimation, serum electrolytes, serum creatinine, serum amylase, uric acid, LFT's, TFT's, ETT and abdominal ultrasound to look for liver texture and for any evidence of fatty change; morphology, texture of kidney and pancreas and other abdominal viscera.
   
3. Total lipid profile which included: Total fasting lipids, Total fasting triglycerides, Total fasting cholesterol, HDL cholesterol and LDL cholesterol.
   

The total number of patients included in the study was 120. All of them were known diabetics. The female to male ratio was 2:1.

Regarding the age group, the majority of our patients were in the age group ranging from 31-60 years. Only 14% were above the age of 60 years.

Regarding the type of diabetes, we found that 15% had IDDM and 85% NIDDM. Regarding the duration of diabetes mellitus 78% of the cases had diabetes mellitus for the last 7-17 years.

The dietary intake in 45% of patients was complex carbohydrates and high fibre diet. 25% had a liking for a fat enriched diet of which females were the majority. 15% were following no dietary restrictions.

Body mass index was evaluated by the following formula in all patients. BMI = weight in kilogram / height in meters(9). 40% had normal body mass index, 15% below normal, while 45% had a body mass index above the normal range.

The triglyceride levels were raised only in 58% patients. 29% patients had only raised serum triglyceride without any clinical evidence of hyperlipidaemia.

Regarding the fasting blood glucose it was found more to be more than 140 mg/dl in 85% of cases. The majority of patients had poor to uncontrolled glycaemic levels.

Renal function tests i.e. blood urea, serum creatinine and electrolytes were carried out to rule out any renal pathology, but they were found within the normal limits. Liver function tests, thyroid functions tests were normal.

In general 44% of the patients had normal total serum lipids, while 56% showed raised levels. Out of 56%, 46% had serum lipid levels in the range of 1000-1500 mg/dl, while the remaining 10% of patients had a level in the range of 1500-2500 mg/dl.

Total fasting serum cholesterol was found normal in 80% patients. 20% had raised serum cholesterol in the range of 251-300 mg/dl. All of these 20% of cases also had triglyceride levels more than 200 mg/dl, so fulfilling the hyperlipidaemic criteria of National cholesterol education programme of the USA.

LDL - cholesterol was found to be normal in 80% of cases while 20% showed a raised level. HDL - cholesterol in 15% of cases was less than 40 mg/dl, who were at a higher risk of IHD, while it was found above 40 mg/dl in the remaining 85% cases.
Hypertriglyceridaemia was found both in IDDM and NIDDM patients. It was more in NIDDM (70%) than IDDM (30%) patients.

In IDDM the majority of patients had mild to moderate hypertriglyceridaemia. The same was the case in NIDDM patients.

In our study, we found that 24% had ischaemic heart disease as evidenced by serial ECGs

Patients with diabetes can have many lipid abnormalities, including elevated levels of very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides; and low levels of high-density lipoprotein cholesterol (HDL-C) (10). These patients have a preponderance of abnormalities in the composition of LDL-C (smaller, denser particles), which increase atherogenicity even if the absolute concentration of LDL-C is not significantly increased. The combination of elevated levels of small, dense LDL-C particles and high triglyceride levels represents a lethal cholesterol abnormality known as pattern B.

About 20% of patients with type 2 diabetes have hypertriglyceridaemia or low HDL-C levels (11). These abnormalities, as well as high VLDL-C levels and high total and VLDL-related triglyceride levels, are powerful risk indicators for CAD in patients with type 2 diabetes. In addition, the combination of elevated total cholesterol level, hypertension, and uncontrolled hyperglycaemia is implicated in the development of nephropathy.

In a study done in Russia, dyslipadaemia was detected in 84% diabetic patients(12). In one European study 40% were hyperlipidaemic according to the criteria of National cholesterol education programme, (cholesterol and triglyceride greater than 200 mg/dl). An additional 23% showed hypertriglyceridaemia(13). In another study hiperlipidaemia was found in 28% of diabetic patients(14).

In our study total fasting lipids of greater than 1000 mg/dl were found in 56% and fasting hypercholesterolaemia and increased LDL cholesterol in 20% of the patients. The values of cholesterol and LDL cholesterol declined from younger to older ages; so these results are in conformity with the previous study(15).

Hypertriglyceridaemia was found to be the commonest dyslipidaemia in this study i.e. 58%; greater than the previous studies. The majority of patients in our study were type II diabetics (70%) as compared to type I (30%). Winocour et al, has shown 40% hyperlipidaemia in IDDM patients. Hypertriglyceridaemia was found predominantly in all the cases while a few had combined hyperlipidaemia, pure hypercholesterolaemia however was not observed in a single case(16).

Hypertriglyceridaemia, which is comparatively more common in NIDDM than IDDM(17) is probably due to increased production and reduced clearance of rich lipoproteins-VLDL(18) . Amongst the NIDDM patients hypertriglyceridaemia is depending upon the variation in the apo E gene, because significantly higher level of VLDL - triglycerides have been found in patients with epsilon 2 heterozygote than in those without the epsilon 2 allele(19). It is further interesting to note that even the 1st degree relatives of NIDDM cases have dyslipidaemia in general and hypertriglyceridaemia in particular(20) . In the number of European studies dislipidaemia is more common in males, beyond 35 years of age(21). But in our study it is more common in females. One factor responsible for this is that they are confined to their housekeeping without any active physical activity.

Exercise has potential benefits for these patients. It not only has a lipid lowering effect but it also potentiates the effect of diet or drug therapy on glucose metabolism in NIDDM patients(22). In our study only 24% were in the habit of taking regular exercise.

The poorer the glycaemic control, the higher the degree of hypertriglyceridaemia. This relationship can be explained by the glucoregulatory and lipolytic actions of insulin, and defect in this can lead to dyslipidaemia more so in NIDDM patients(23). If good glycaemic control is achieved then not only the size of VLDL particle is reduced but also increases in the concentration of apo - B protein fraction of VLDL takes place. These changes in turn lead to increased clearance of VLDL particles and ultimately dislipedaemia reverts(24).In one study 28% of diabetic patients had hyperlipidaemia with a poor glycaemic control as defined by a glycated hemoglobin value of more than 10%(14). In our study 58% of the total patients had poor glycaemic control as assessed by serial 2 hours post prandial glucose estimation according to WHO criteria(25). All of these showed mild to severe dislipidaemia.

In WHO criteria, levels less than 150 mg/ dl were taken as good, between 150-200 mg/ dl as permissible and above 200 mg/dl as poor glycaemic control.

Apart from the blood glucose estimation glycaemic control can be monitored by estimation of glycated HbAIC, glycated fructosamine and glycated serum albumin. Glycated HbAIC comprises 4-6% of the total haemoglobin. Levels less than 10% reflect a good glycaemic control over the preceding 8- 12 weeks(26). However, glycated serum albumin can be a more reliable marker of short term glycaemic control in IDDM than fructosamine(27).

Diabetic patients with hyperlipidaemia frequently develop atherosclerosis. Superoxide, which is present in diabetic patients with hypertrigly ceridaemia, is suspected to play an important role in the initiation of this atheroselerosis. (28) Other atherogenic factors specific to diabetes mellitus, however are concomitantly present which potentiate the process of atherosclerosis. Both low HDL and high triglyceride levels are frequently associated with other coronary risk factors. Correction of both, may reduce coronary artery disease risk without fear of adverse side effects. (29)

In various studies the plasma triglyceride level exceeding 3 m.mole/L (270 mg/dl) is universally accepted as hypertriglyceridaemia in diabetes mellitus(14) and the greater levels are positively correlated with the increased risk of coronery artery disease(30,31). It is noteworthy that triglyceride levels greater than 2 mmol/L are the angiographically proven marker of coronary artery disease(32).

In long term follow up, for more than 10 years, patients with impaired glucose tolerance tests and or frank diabetes mellitus, it was observed that the mortality rate with respect to IHD was remarkably high in those having moderately severe hyperlipidaemia than those with border line(33). Silent myocardial infarction which is seen in 15-24% of patients with diabetes mellitus(34) becomes even more common in the presence of long standing moderate to sever hyperlipidaemia. In our study 24% had ischaemic heart disease. Their lipid profile showed mild to moderate hypertriglyceridaemia (200- 400 mg/dl, while total cholesterol, LDL cholesterol and HDL cholesterol were all normal.

Hypertiglyceridaemia is the most common lipid abnormality in diabetes mellitus, which is more common in NIDDM than IDDM.

Early diagnosis, good glycaemic control and dietary modification are usually enough for prevention and treating hypertriglyceridaemia in diabetes mellitus.