Introduction
In the modern world, the growing incidence of type 2 diabetes mellitus (T2DM) is a critical problem. Most subjects with T2DM have insulin resistance and are at increased risk of developing cardiovascular disease (CVD). Excess morbidity and mortality in T2DM are mainly due to dyslipidemia. Postprandial triglyceridemia is a distinct component of diabetic dyslipidemia.1 ostprandial hypertriglyceridemia results in a proatherogenic environment which leads to atherosclerosis and macrovascular complications in type 2 diabetes mellitus. It is believed that atherosclerosis is a postprandial phenomenon with respect to lipids, as we are in the postprandial state for most of the day2,3 Increased glucose production in the liver occurs early in the course of diabetes, and it is likely in skeletal muscles after the onset of the insulin secretory abnormalities and the insulin resistance.4 Due to the insulin resistance in the adipose tissue and obesity, the free fatty acid (FFA) flux from the adipocytes is increased, which in turn leads to an increase in lipid [very low-density lipoprotein (VLDL) and triglycerides] synthesis in the hepatocytes. This is responsible for the dyslipidaemia which is found in type2 diabetes mellitus [elevated triglycerides, reduced HDL, and increased low-density lipoprotein (LDL) particles.4 Individuals with type 2 diabetes mellitus are at increased risk of developing microvascular and macrovascular complications. Increased postprandial glucose (PPG) concentrations contribute to suboptimal glycemic control. Postprandial hyperglycemia is one of the earliest abnormalities of glucose homeostasis associated with type 2 diabetes mellitus and is markedly exaggerated in diabetic patients with fasting hyperglycemia.5,6,7 Correcting the postprandial hyperglycemia may form a key part of the strategy for the prevention and management of CVDs in diabetes.
It is not clearly known whether diabetic patients with macrovascular diseases have greater abnormalities of postprandial TG metabolism than those without.In view of the above said the study was carried out to find out the characteristics of postprandial lipid levels in patients with type 2 diabetes mellitus and its impact on the vascular complications.
Objective of The Study
To correlate fasting and postprandial dyslipidemia with macrovascular complications of diabetes
Material and Methods
This is a descriptive cross-sectional study.
Patients who were in the age group of 35-65 years, admitted in the Department of Medicine, RRMCH from November 2017 for next 18 months with Diabetes Mellitus who met a predefined inclusion and exclusion criteria were studied.
The study was initiated after obtaining clearance from the institution's ethical committee.
Inclusion criteria
All type 2 DM patients who were in the age group of 35-65 years on regular treatment with OHA which had a duration of diabetes of more than 5 years in medicine OPD, diabetic clinic and wards.
Exclusion criteria
1. Type I DM patients
2.Patients with congenital hyperlipidemia
3.Diabetic patient on the hypolipemic drug.
4.Patients on insulin therapy
5.Gestational Diabetic patients
6.Patients with thyroid disease
7.Patients not willing for the study
Sample
50 cases of type 2 diabetes mellitus with abnormal fasting lipid profile(one or more lipid parameter) and 50 controls of type 2 diabetes mellitus with normal fasting lipid profile.
Diabetes is diagnosed by world health organization (WHO) criteria
Fasting plasma glucose (FPG)-126 mg/dl(7.0 mmol/l )or,
75 g oral glucose tolerance test (OGTT) with fasting plasma glucose>126 mg/dl (7.0
mmol/l)and/or 2 hours plasma glucose >200 mg/dl (11.1 mmol/l) or,
Glycated hemoglobin (HbA1c) > 6.5mg/dl or 48 mmol/mol, or
Random plasma glucose >200 mg/dl (11.1 mmol/l) in the presence of classical diabetes symptom
Plasma glucose is measured by Randox autoanalyser using the colorimetric method without deproteinisation using glucose oxidase enzyme.
Dyslipidaemia: Abnormal lipid profile includes the following either singly or in combination, triglyceride (TG) levels >150 mg/dl, high density lipoprotein cholesterol (HDL-C) (for men < 40 mg/dl and women > 50 mg/dl), low density lipoprotein cholesterol (LDL-C) >100mg/dl.
Lipid profile using RANDOX autoanalyser. All parameters expressed in milligram /decilitre. Cut-off values according to NCEP ATP III guidelines.[7]
NCEP ATP III criteria for lipids
Table 1
LDL Cholesterol (mg/dL)
|
<100 |
Optimal |
|
100-129 |
Near optimal/above optimal |
|
130-159 |
Borderline high |
|
160-189 |
High |
|
>190 |
Very high |
Also, considered abnormal is an elevated total serum cholesterol level >200 mg/dl
Study protocol
Subjects fulfilling inclusion criteria were selected for the study. Each subject made two visits to the study hospital during which medical history, physical examination, systemic examinations and relevant investigations were carried out and they were advised to take a low fat diet consisting of 60% carbohydrates,25% fats and 15% proteins divided into 3 meals. Complete clinical history including name, age, sex, occupation, residence, presenting symptoms, duration of diabetes was noted. The general examination includes vitals i.e. pulse, supine and standing blood pressure at 3 minutes, general body survey, waist to hip ratio will be recorded. Systemic examination of cardiovascular, respiratory, gastrointestinal and CNS was done. Patients were examined, investigated and evaluated for specific complications of diabetes.
Following selection, the following was done
History, (including family history) to judge the likelihood of a familial lipid disorder
A complete clinical examination (including fundus)
CBC, ESR, Peripheral smear.
Renal function test, Liver function test, TSH, Serum Electrolytes
Fasting and Postprandial blood sugars, HbA1C.
Urine Routine,
BT, CT, PT/INR, aPTT
ECG and 2D Echo
CT scan / MRI scan of the brain.
Chest X-ray (PA view).
USG Abdomen
Fasting Lipid Profile, Fasting LDL, LDL
Total cholesterol
Chylomicrons, VLDL & HDL are eliminated by cholesterol esterase and oxidase then the specific measurement of LDL cholesterol is made after the release of LDL by detergents.
LDL- Cholesterol
Triglycerides: GPO-PAP method. Triglycerides are determined after enzymatic hydrolysis with lipases and indicator quinonimine is formed is measured by colourimetric method.
HDL-Cholesterol: Chylomicrons, VLDL & LDL are eliminated by cholesterol esterase and oxidase then the specific measurement of HDL cholesterol is made after the release of HDL by detergents.
VLDL cholesterol: Calculated from total cholesterol –( LDL+ HDL cholesterol).
The data was collected in pre-prepared proforma and then transferred to a master chart for analysis.
Sample Size Estimation Calculation
Sample size
This is a descriptive cross-sectional study which was done in the Department of Medicine, RRMCH, Bangalore.
50 cases of type 2 diabetes mellitus with abnormal fasting lipid profile (one or more lipid parameter) and 50 controls of type 2 diabetes mellitus with normal fasting lipid profile.
Data and Statistical Analysis
The data collected was analyzed using mean, mode for demographic data and frequency percentage for the analysis of the clinical data.
Statistical Analysis was done using SPSS software version 23.0. A ‘p’ value less than 0.05(p<0.05) is considered significant.
The various measures of central tendencies and graphical representations were used to analyze the data.
The data was analyzed using SPSS version 20. Mean and standard deviation will be applied between two groups. 't' test was applied to know the mean difference between two groups.
Observation and Results
Table 4
Age distribution among patients in the study
In the present study, when we evaluated the age distribution of the cases in the study we found that the most common age group was between the ages of 56-65 years, 39 patients belonged to this group with 22 patients in the test and 17 patients in the controls. 38 patients belonged to 46-55 years age group with 17 patients in the test and 21 patients in the controls. 23 patients belonged to 35-46 years age group with 11 patients in the test and 12 patients in the control respectively.
Table 5
Distribution of gender in study
|
Gender |
Number |
Percentage |
|
Male |
61 |
61.00% |
|
Female |
39 |
39.00% |
|
Total |
100 |
Table 6
Distribution of occupation among patients in the study
Table 7
Distribution of residence among the subjects in the study
|
Locality |
Number |
Percentage |
||||
|
Cases |
Controls |
Total |
Cases |
Controls |
Total |
|
|
Rural |
15 |
12 |
27 |
30.00% |
24.00% |
27.00% |
|
Urban |
35 |
38 |
73 |
70.00% |
76.00% |
73.00% |
|
Total |
50 |
50 |
100 |
100.00% |
100.00% |
100.00% |
Table 8
Distribution of addictions among patients in the study
Table 9
Distribution of the patients according to duration of diabetes in the study
Table 10
Distribution of the cases in the study based on treatment
Table 11
Comparison of mean fasting lipid parameters
Descriptive Statistics
Table 12
Comparison of mean postprandial lipid parameters
Table 13
Comparison of mean lipid parameters within cases
Table 14
Comparison of mean lipid parameters with in controls
Table 15
Comparison of fbs and ppbs with in controls
|
Cases |
Controls |
P Value |
|
|
FBS |
142.09 |
122.17 |
0.00 |
|
+45.86 |
+33.42 |
||
|
|
212.35 |
181.96 |
0.00 |
|
+67.97 |
+33.77 |
||
|
P Value |
0.00 |
0.00 |
Table 16
Comparison of hbaic among cases and controls
|
Group |
Minimum |
Maximum |
Mean |
Std.- Deviation |
||
|
Cases |
HBA1C |
50 |
5.7 |
8.4 |
7.142 |
0.8318 |
|
controls |
HBA1C |
50 |
4.6 |
6.2 |
5.554 |
0.4367 |
Table 17
Comparison of macrovascular complications among cases and controls
|
Macrov- ascular |
Frequency |
Percent |
P value |
||
|
complications |
Cases |
controls |
Cases |
Controls |
|
|
NIL |
13 |
41 |
26 |
82 |
<0.05 |
|
CVA |
6 |
1 |
12 |
2 |
<0.05 |
|
IHD |
11 |
3 |
22 |
6 |
<0.05 |
|
PVD |
20 |
5 |
40 |
10 |
<0.05 |
|
Total |
50 |
50 |
100 |
100 |
|
Table 18
Comparison of type of strokes among cases and controls
|
Type of strokes |
Cases |
Controls |
|
Ischemic stroke |
5 |
1 |
|
Hemorrhagic stroke |
1 |
0 |
|
Total |
||
|
6 |
1 |
Discussion
In 2000, India was the world capital of diabetes with the highest number of people with diabetes mellitus (31.7 million) followed by China (20.8 million) & the United States (17.7 million) in second and third place respectively. Cardiovascular disease (CVD) is a significant cause of illness, disability, and death among individuals with diabetes. The macrovascular complications of diabetes— Coronary Heart Disease (CHD), Cerebrovascular Accidents (CVA), and Peripheral Vascular Disease (PVD)— all being different facets of the same vascular damage — account for more than 70% of all deaths in individuals with diabetes. CVD events are four times more common in individuals with diabetes, occur at a younger age, and have a much higher case fatality rate, this is more so in Indians. Coronary Artery Disease in Indians (CADI) is a phenomenon by itself. In fact, people with diabetes and no history of vascular disease have the same risk of having a heart attack or dying of vascular disease as non-diabetic individuals with a prior history of cardiovascular disease.Lipid and lipoprotein abnormalities are common in the diabetic population due to the effects of insulin deficiency and insulin resistance on key metabolic enzymes.
In a study by Puthenveedu et al (2017) at Madhurai medical college, India found that persistent postprandial hypertriglyceridemia may result in a proatherogenic environment leading to atherosclerosis and macrovascular disease in type 2 diabetes subjects. LDL oxidation in the postprandial state is affected by an acute increase in glucose levels. Thus, oxidative modification of LDL cholesterol may contribute to higher CVD risk in diabetic patients, and elevated triglyceride levels may contribute to the rapid LDL oxidation seen in Type 2 DM.Due to lack of studies including these criterias in cases and controls distribution, comparison was not possible in some points. In the present study 100 type 2 diabetes mellitus patients, divided into 50 cases and 50 controls satisfying inclusion criteria were considered. The study comprises 61 male patients & 39 female patients. Prevalence of diabetes was highest in the age group 56-65 years 39out of 100. Sarha Wild et al in their study noted the highest prevalence of type 2 diabetes in the age group of 41-64 years in developing countries (Finding consistent with our study) while in developed countries it is highest in people >65 years.In another study by Santosh YL et al, they noted the highest prevalence of diabetes in the age group 61-70 years(24.92%) while age group 51-60 had 21.42% cases.
In our study the maximum number of patients had a duration of diabetes for >10years.30 patients had a duration of diabetes between 1-5 years.39 and 30 patients had diabetes duration between 10 -15 years and >15 years respectively.In this study, distribution of fasting dyslipidemia (cases) is more in 56-65yrs age group, while in study carried out Kusum Bali, et al the distribution of dyslipidemia among the different age groups was almost similar: 82.6% in < 45 years, 82.9% in 45-60 years and 83.7% in > 60 years, the difference was not statistically significant.61In our study we found the distribution of fasting dyslipidemia is slightly higher in males as compared to females, findings are consistent with the study by Kusum Bali, et al, where they found dyslipidemia is more in males (133 males out of 285 DM type 2 patients).In the present study, we found fasting dyslipidemia was maximum in both cases and controls with the duration of diabetes >10 yrs.In the present study IHD was found in 14 out of 100 patients,11 in cases and 3 in controls i.e. 22% and 6% respectively. Evidence of IHD was found more in cases compared to controls, statistical significance was found (p<0.05). In a study carried out by Angelo Avogaro, et al they found that the age-standardized incidence rate (per 1,000 person/years) of first CHD event was 28.8 in men and 23.3 in women.
In a study carried out by R.P. Agrawal, et al in 4067 patients of DM 2 they found that the prevalence of CHD was 12.4% and the risk of CHD in known Type 2 diabetic patients was higher in men than in women. Of the diabetic men 60% showed high (20–40%) or very high (>40%) risk of CHD, while 56% of the women had values compatible with moderate (10–20%), mild (5–10%) or low (<5%) risk of CHD (p<0.05). In a study carried out by Deepa D. V., et al in Bellary, Karnataka. in 100 newly diagnosed DM 2 patients they found the prevalence of peripheral vascular disease 11%.64In a study carried out by R.P. Agrawal, et al in 4067 patients of DM 2 they found PVD was present in 735 patients, prevalence 18.1%. In this study we found CVA in 7 out of 100 patients, in cases evidence of CVA was found in 6 patients out of 50 i.e. 12% and in controls it was found in 1 patient out of 50 patients i.e. 2%. Evidence of CVA is found more in cases compared to controls with statistical significance. (p<0.05).The overall prevalence of stroke found was 7 out of 100 patients (7%) out of which 6 patients had an ischemic stroke and 1 had a hemorrhagic stroke.
In a study carried out by Nafisa C Vaz, et al To determine the prevalence of diabetes mellitus (DM) and its associated diabetic complications in rural Goa, India they found Among the total 1,266 study participants about 130 (10.3%) were diabetics And prevalence of cerebrovascular accidents (CVAs) was 6.9%. In a study carried out by Seppo Lehto, et al they concluded that the risk of stroke in non-insulin dependent diabetes mellitus(NIDDM) men was about threefold and in NIDDM women fivefold higher than that in corresponding nondiabetic individuals. Low levels of HDL cholesterol (<0.90 mmol/L), high levels of total TGs (>2.30 mmol/L), and the presence of hypertension(HTN) were associated with a twofold increase in the risk of stroke mortality or morbidity.
In a study carried out by Jasmina Djelilovic-Vranic, et al Ischemic stroke was confirmed in 78.0%, of which 32% were lacunar infarcts and 22% hemorrhagic. The most common risk factors were hypertension 85%, then smoking in 65%, diabetes mellitus in 39.0%, in 27.38% dyslipidemia, the previous stroke in 26.69%, in 23.57% arrhythmia. In the baseline sample, 30.06% of patients had previously diabetes mellitus and in 8.94% the diabetes was diagnosed during hospitalization, while dyslipidemia was known from earlier in 22.0% and in 5.38% cases was detected during the hospitalization.
Summary
This study was conducted in the department of medicine, Rajarajeswari medical college and hospital Bangalore. In the present study 100 type 2 diabetic patients, divided into 50 cases and 50 controls satisfying inclusion criteria were considered.
The findings are summarized as follows:-
A maximum number of diabetic individuals belonged to the age group 56-65 years(39 out of 100patients i.e. 41%). A maximum number of cases were in the age group of 56-65 years(22 out of 50 patients i.e.44%), while the maximum number of controls belonged to 46-55years age group (21 out of 50patients i.e. 42%).
The maximum number of patients belonged to urban areas (73 out of 100 patients i.e.73%). Both in control and cases maximum no of patients were from urban areas( 38 and 35 patients in controls and cases respectively).
Past history of HTN, IHD, PVD and CVA were significantly more in cases as compared to controls, statistical significance was found (P<0.05).
More patients in cases were on irregular anti-diabetic treatment as compared to controls (15 patients in cases and 2 in controls).
IHD changes were found in 8 cases and 3 controls, LVH by voltage criteria was found in 15 cases and 8 controls. IHD changes found in cases and controls are 16% and 6% respectively. LVH changes found in cases and controls are 30% and 16% respectively.
Abnormal 2D Echo findings in our study were mainly IHD and LVH. IHD was found in 11 cases and 3 controls, LVH was found in 18 cases and 10 controls. IHD changes found in cases and controls are 22% and 6% respectively. LVH changes found in cases and controls are 36% and 20% respectively.
There was a significant elevation of mean values of total serum cholesterol, LDL and TG of cases and controls in the postprandial state compared to their fasting state, statistical significance was found (P<0.05).
Mean values of total serum cholesterol, LDL and TG of cases in fasting state were significantly more compared to controls in fasting state, statistical significance was found (P<0.05).
Mean values of total serum cholesterol, LDL and TG of cases in the postprandial state were significantly more compared to controls in the postprandial state, statistical significance was found (P<0.05).
Mean values of both FBS and PPBS in cases were higher compared to controls (P<0.05). Mean values of PPBS in cases and controls were significantly more compared to their respective FBS values (P<0.05).
The mean HbA1c values in cases were higher(7.142) compared to controls (5.554).
Ischemic Heart disease was found in 14 patients i.e.14% of the study group. In cases, it was found in 11 patients and in controls, it was found in 3 patients i.e. 22% and 6% respectively. The occurrence of IHD was more in cases compared to controls with statistical significance(p<0.05).
Peripheral vascular disease in our study was found in 25 patients i.e.25% of the study group. In cases, it was found in 20 patients and in controls, it was found
Stroke in our study is found in 7 patients i.e. 7% of the study group. In cases, it was found in 6 patients and in controls, it was found in 1 patient i.e. 12% and 2% respectively. The occurrence of CVA was more in cases compared to controls with statistical significance(p<0.05).Ischemic strokes were more common than haemorrhagic strokes.
Conclusion
Prevalence of diabetes was highest in the age group 56-65 years in our hospital.
As the duration of diabetes increases, there is an increased prevalence of dyslipidemia in the cases.
Past history of HTN, IHD, PVD and CVA were found significantly more in subjects with fasting and postprandial dyslipidemia (cases) compared to those without(controls).
Patients on irregular treatment (63%) were more in the study group(cases) compared to controls. So it could be said that patient not on regular treatment are more prone to have dyslipidemia. (fasting as well as postprandial).
There was a significant increase in total serum cholesterol, LDL and TG in postprandial states of cases compared to that in controls, so it could be said that diabetic patients with fasting dyslipidemia are more prone to have dyslipidemia in the postprandial state.
Cases were having significantly higher FBS and PPBS compared to the controls, so it could be said that as blood sugar increases the occurrence of dyslipidemia increases.
HbA1c was significantly higher in cases compared to controls, so it could be said that as HbA1c increases there is an increase in the occurrence of dyslipidemia.
It could be said that there is an increase in the occurrence of postprandial dyslipidemia with increasing age, irregular treatment, increase in HbA1c, FBS ,PPBS and with the past history of HTN, CVA, PVD and IHD.
All macrovascular complications (IHD, CVA, PVD) were found more in the case compared to controls with statistical significance. So it could be said that there is an increase in the occurrence of macrovascular complications with an increase in postprandial dyslipidemia.
It could be said that there is an increase in the occurrence of macrovascular complications with an increase in postprandial dyslipidemia, increasing age, irregular treatment and increase in HbA1c, FBS and PPB
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