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ISSN 2723-6927-e ISSN 2723-4339
The Relationship Between Glycemic Control And Lipid Profile In Patients With Type 2 Diabetes
Mellitus In Bangli General Hospital
Made Ayu Agustia Pradnyani1*,
I Ketut Sutarjana2
1*Dokter Umum, Rumah Sakit Umum Daerah
Bangli, Bali, Indonesia
2Departemen Ilmu Penyakit Dalam, Rumah Sakit Umum Daerah Bangli,
Bali,Indonesia
Email: [email protected]
Type 2 Diabetes Mellitus (DM) is prone to diabetic dyslipidemia, which
is a factor in increasing the risk of cardiovascular disease complications.
This study aims to determine the relationship between glycemic control and
lipid profiles in patients with type 2 DM. A cross-sectional study was
conducted at the Internal Medicine Clinic of Bangli General hospital from
January 2023 to December 2023, involving 60 type 2 DM patients who met the
inclusion criteria. Patients were grouped into those with good glycemic control
(HbA1c < 7%) and poor glycemic control (HbA1c ≥ 7%).
Lower levels of total cholesterol (160.444 � 30.608 mg/dl vs. 203.476 � 45.471
mg/dl; p = 0.001), triglycerides (125.500 � 56.019 vs. 202.047 � 91.568; p =
0.002), and low-density lipoprotein (LDL-C) (93.072 � 28.443 vs. 131.571 � 44.590;
p = 0.001) were observed in type 2 DM patients with good glycemic control.
Higher levels of high-density lipoprotein (HDL-C) (50.022 � 14.050 vs. 41.152 �
12.619; p = 0.019) were observed in type 2 DM patients with good glycemic
control. Statistical analysis revealed a positive correlation between total
cholesterol levels (r = 0.277; p = 0.032), triglycerides (r = 0.386; p =
0.002), and LDL-C (r = 0.357; p = 0.005) with HbA1c levels. There was a
negative correlation between HDL-C (r = -0.366; p = 0.004) and HbA1c levels.
The significant correlation between HbA1c and lipid profiles highlights the
importance of glycemic control in patients with type 2 DM. This can be
explained by the pathogenesis of advanced-stage type 2 DM. There is a positive
correlation between glycemic control (HbA1c) and total cholesterol,
triglycerides, and LDL-C. There is a negative correlation between glycemic
control (HbA1c) and HDL-C.
Keywords: Diabetes Mellitus, Cholesterol,
HDL-C, LDL-C, Triglycerides
Introduction
Diabetes mellitus (DM) is a group of
metabolic diseases characterized by hyperglycemia due to defects in insulin
secretion, insulin action, or both (PERKENI, 2021). Currently, DM is one of the most
prevalent chronic diseases worldwide (Sapra A BP, 2023). According to epidemiological studies,
there are currently 387 million people with DM globally, and this number is
expected to increase to 592 million by 2035 and 642 million by 2040 (Zheng et al., 2018).
HbA1c (glycated hemoglobin) is a type of
hemoglobin that reflects the average plasma glucose concentration over three
months and has been recommended by PERKENI as a long-term glucose evaluation
for patients with type 2 DM (PERKENI, 2021) (Goyal et al., 2021)�� (WHO, 2011) (Alzahrani et al.,
2019). Elevated HbA1c levels are independently associated
with an increased risk of both macrovascular and microvascular complications
and are linked to metabolic syndrome (WHO, 2011) (PB PERKENI, 2021). HbA1c is not only an indicator of
glycemic control but also a predictor of dyslipidemia (Goyal et al., 2021) (Setiati et al., 2014) (Kumar et al., 2022).
Type 2 DM patients are prone to diabetic
dyslipidemia, a lipid metabolism disorder that contributes to the increased
risk of cardiovascular disease complications. Diabetic dyslipidemia includes
both quantitative and qualitative lipoprotein abnormalities, resulting in a
shift towards an atherogenic lipid profile (Huang et al., 2021) (Reza et al., 2023). Hyperglycemia, insulin resistance, and
relative insulin deficiency observed in type 2 DM patients likely contribute to
lipid changes, as insulin plays a crucial role in regulating lipid metabolism (Huang et al., 2021).
Given the various empirical evidence
presented, the relationship between glycemic control and lipid profiles needs
further investigation. The evidence regarding the relationship between glycemic
control and lipid profiles in type 2 DM patients is still conflicting.
Therefore, this study aims to determine the relationship between glycemic
control and lipid profiles in type 2 DM patients at Bangli General hospital.
Reseach Method
This study is an analytical correlational study using a
cross-sectional approach to examine the relationship between glycemic control
(HbA1c) and lipid profiles in type 2 DM patients. The study was conducted at
the Internal Medicine Clinic of Bangli General hospital from January 2023 to
December 2023. Data were collected from patient medical records. Ethical
approval was obtained from the Health Research Ethics Committee of Bangli
General hospital (No.400.7.22.2/1024/RSUD) to ensure that the study was conducted
according to proper procedures. Consent was obtained from the subjects after
explaining the details of the study in Indonesian and/or the local language
(Balinese). Confidentiality was maintained in this study.
The target population consists of all outpatients diagnosed with
type 2 DM, while the accessible population includes type 2 DM patients at Bangli
General hospital, particularly those at the Internal Medicine Clinic who meet
the inclusion and exclusion criteria. Inclusion criteria: patients diagnosed
with type 2 DM with medical record data including HbA1c and lipid profiles
(total cholesterol, HDL-C, LDL-C, triglycerides); Exclusion criteria: type 2 DM
patients without medical record data of HbA1c and lipid profiles (total
cholesterol, HDL-C, LDL-C, triglycerides), type 2 DM patients receiving
previous dyslipidemia therapy (statins, fibrates, niacin), pregnant patients,
patients with thyroid disease, chronic liver disease, chronic kidney disease,
and other endocrine disorders. The minimum sample size required is 51 people (Dahlan., 2016).
The sampling technique used in this study is non-probability
sampling, specifically purposive sampling based on the inclusion and exclusion
criteria. The purposive sampling yielded a sample size of 60 people, which met
the study's requirements.
Dependent variable: the dependent variable in this study is the
lipid profile, including total cholesterol, triglycerides, LDL-C, and HDL-C,
measured on a numerical scale. Independent variable: the independent variable
in this study is glycemic control measured through HbA1c levels. HbA1c levels
will be categorized into two groups. Patients with HbA1c <7% are categorized
as having good glycemic control, while patients with HbA1c ≥7% are
categorized as having poor glycemic control. The measurement scale used is numerical.
Operationally, type 2 DM patients are defined as patients
diagnosed with type 2 DM at the Internal Medicine Clinic of Bangli General
hospital between January 2023 and December 2023. The assessment of patients is
based on their medical records at the Internal Medicine Clinic of Bangli
General hospital. Glycemic control is assessed using HbA1c laboratory results,
which reflect the average plasma glucose levels. The lipid profile is assessed
by measuring total cholesterol, triglycerides, LDL-C, and HDL-C levels.
Statistical analysis was performed with data homogeneity tests
followed by comparative and correlation tests. Comparative tests of total
cholesterol, triglycerides, LDL-C, and HDL-C levels were conducted between the good glycemic control and poor glycemic control groups. Comparative tests were conducted using
the independent T-test. Correlation tests assessed the relationship between
glycemic control (HbA1c) and total cholesterol, triglycerides, LDL-C, and HDL-C
levels. The correlation test used is Pearson's correlation if the data
distribution is normal; otherwise, the alternative test, Spearman's
correlation, is used. All tests are considered significant if the p-value <
0.05. Data analysis was performed using SPSS software version 26.
Results and Discussion
In this study, out of 60 type 2 DM patients, 18 were in the good
glycemic control and
42 were in the poor glycemic control. Among the 18 patients with good glycemic
control, 7 (38.9%) were male, and 11 (61.1%) were female. In the poor glycemic
control 42
patients, 24 (57.1%) were male, and 18 (42.9%) were female. Regarding age
characteristics, the average age of patients with good glycemic control and poor glycemic
control groups was 66.277 years and 60.170 years, respectively. Patients with good
glycemic control had an average HbA1c level of 5.991, while the average HbA1c
level in the poor glycemic control group was 9.471. The characteristics of the
respondents are shown in Table 1.
Table 1. Respondent
Characteristics
|
Characteristics |
HbA1c |
||
|
Good glycemic control (<7%) n = 18 |
Poor
glycemic control (≥7%) n = 42 |
p-value |
|
|
Gender, n (%) |
|
|
0.201 |
|
Male |
7 (38.9) |
24 (57.1) |
|
|
Female |
11 (61.1) |
18 (42.9) |
|
|
Average Age |
66.277 |
60.170 |
0.043 |
|
Average HbA1c |
5.991 |
9.4710 |
0.000 |
A comparative analysis of the lipid profiles of type 2 DM patients
between good glycemic control and poor glycemic control groups was conducted using an independent T-test. The results of
this study showed that patients in the good glycemic control had
lower levels of total cholesterol, triglycerides, and LDL-C, while good glycemic control had higher HDL-C levels. The differences in lipid profiles based
on glycemic control are presented in Table 2.
Table 2. Differences in Lipid
Profile Levels Based on Glycemic Control
|
Variable |
HbA1c |
||
|
Good glycemic control (<7%) n = 18 |
Poor glycemic
control (≥7%) n = 42 |
p-value |
|
|
Total Cholesterol |
160.444 � 30.608 |
203.476 � 45.471 |
0.001 |
|
Triglycerides |
125.500 � 56.019 |
202.047 � 91.568 |
0.002 |
|
K-LDL |
93.072 � 28.443 |
131.571 � 44.590 |
0.001 |
|
K-HDL |
50.022 � 14.050 |
41.152 � 12.619 |
0.019 |
Before conducting the correlation test between glycemic control
(HbA1c) and lipid profiles, a normality test was performed using the
Kolmogorov-Smirnov test, as the sample size in the study was >50. In the
Kolmogorov-Smirnov test, HbA1c (p=0.200), total cholesterol (p=0.200), and
LDL-C (p=0.200) data were normally distributed, whereas triglycerides (p=0.000)
and HDL-C (p=0.040) data were not normally distributed, as shown in Table 3.
Table 3. Results of Normality Test for Glycemic Control (HbA1c)
and Lipid Profile
|
Variable |
Sig. |
Description |
|
HbA1c |
0.200 |
Normal |
|
Total Cholesterol |
0.200 |
Normal |
|
Triglycerides |
0.000 |
Not Normal |
|
K-LDL |
0.200 |
Normal |
|
K-HDL |
0.040 |
Not Normal |
The correlation test between glycemic control (HbA1c) and lipid
profiles was conducted using Pearson�s correlation for normally distributed
data and Spearman�s correlation for non-normally distributed data. A weak
positive correlation was found between HbA1c and total cholesterol,
triglycerides, and LDL-C. A positive correlation indicates a direct
relationship; thus, it can be concluded that the higher the HbA1c level, the
higher the total cholesterol, triglycerides, and LDL-C levels. A weak negative
correlation was found between glycemic control (HbA1c) and HDL-C. A negative
correlation indicates an inverse relationship; thus, it can be concluded that
the higher the HbA1c level, the lower the HDL-C level. The results of the
correlation test between glycemic control (HbA1c) and lipid profiles are
presented in Table 4.
Table 4. Results of Correlation Test between Glycemic
Control (HbA1c) and Lipid Profile
|
Relationship |
Sig. |
Correlation
Coefficient |
|
HbA1c with Total Cholesterol |
0.032 |
0.277 |
|
HbA1c dengan K-LDL |
0.005 |
0.357 |
|
HbA1c with Triglycerides |
0.002 |
0.386 |
|
HbA1c dengan K-HDL |
0.004 |
-0.366 |
Discussion
Patients with type 2 diabetes mellitus (DM) are vulnerable to
diabetic dyslipidemia, a lipid metabolism disorder that encompasses not only
quantitative but also qualitative lipoprotein abnormalities, leading to a shift
towards an atherogenic lipid profile. The lipid abnormalities in type 2 DM are
likely due to hyperglycemia, insulin resistance, and relative insulin
deficiency observed in these patients. Dyslipidemia is a predictor of
cardiovascular disease (Huang et al., 2021) (Reza et al., 2023).
In this study, it was found that patients with type 2 DM with good
glycemic control
(HbA1c < 7%) had lower levels of total cholesterol, triglycerides, and LDL-C
compared to those with poor glycemic control (HbA1c ≥ 7%). This finding is consistent
with a study by Handayani et al. (2023), which showed that total cholesterol,
triglycerides, and LDL-C levels were lower in the good glycemic control group
(Reza et al., 2023). This result is also in line with studies by Yudha et al., (2021) and (Artha et al., 2019).
Based on the correlation test results, a significant positive
correlation was found between glycemic control (HbA1c) and total cholesterol (r
= 0.277; p = 0.032), triglycerides (r = 0.386; p = 0.002), and LDL-C (r =
0.357; p = 0.005). The strength of the correlations is relatively low. This
relationship pattern can be explained by the consistency of the results with
previous studies or by using a pathophysiological approach to explain the
relationship between glycemic control and lipid profile.
The results of this study are consistent with a study by Susilo et
al. (2020), which found a significant relationship between HbA1c levels and
total cholesterol levels in type 2 DM patients (p=0.030; r= +0.314) (Susilo et al., 2020). A similar study by Nnakenyi et al., (2022) also found a positive relationship between HbA1c and total
cholesterol (r = 0.406, p <0.05), triglycerides (r = 0.273, p <0.05), and
LDL-C (r = 0.409, p < 0.05). A study by Artha et al. (2019)
involving 140 type 2 DM patients also showed a similar relationship, with
positive correlations between HbA1c and total cholesterol, triglycerides, and
LDL-C (r=0.472; r=0.276;r=0.679) (Artha et al., 2019).
Patients with type 2 DM experience a decrease in plasma
campesterol levels (a marker of cholesterol absorption) and an increase in
plasma lathosterol levels (a marker of cholesterol synthesis). This mechanism
underlies the changes in cholesterol homeostasis. The expression of SREBP2
(which codes for sterol regulation, a factor regulating uptake and synthesis)
is increased in patients with type 2 DM (Verg�s, 2015).
Hypertriglyceridemia is the most common serum lipid disorder found
in DM patients. The increase in plasma triglyceride levels in type 2 DM
patients is largely due to an increase in the number of VLDL, particularly
large VLDL1 particles, and the delayed catabolism of VLDL leads to an increase
in the VLDL pool. Decreased VLDL catabolism due to insulin resistance can lead
to decreased lipoprotein lipase (LPL) activity, resulting in reduced catabolism
of chylomicrons and VLDL, leading to more severe hypertriglyceridemia. Other
mechanisms, such as de novo lipogenesis, also contribute to the increase in
plasma triglycerides in type 2 DM (Verg�s, 2015) (Huang et al., 2021).
In type 2 DM patients, LDL-C also increases. This is due to a
significant decrease in LDL-C catabolism, resulting in a longer duration of
LDL-C in the plasma, which can increase lipid deposition in the arterial walls.
Another mechanism is a significant reduction in the number of cell surface LDL
B/E receptors and decreased affinity of LDL-C to its receptors due to glycation
of ApoB. Type 2 DM patients also experience an increase in oxidized LDL-C in
the plasma. Oxidized LDL-C is formed from triglycerides that are abundant in
VLDL, which exchange with cholesterol esters (CE) from LDL-C in the
circulation. This results in triglyceride-rich but cholesterol ester-poor LDL,
producing small dense LDL, known as small dense LDL particles, which are highly
atherogenic (Susilo et al., 2020) (Artha et al., 2019).
The correlation test results showed a significant negative
correlation between glycemic control (HbA1c) and HDL-C (r=-0.366; p = 0.004).
The strength of the correlation is relatively low. Similar results were
obtained in a study by Huang et al. (2021), which involved 3171 type 2 DM
patients and found a negative relationship between HbA1c and HDL-C (p= 0.044) (Huang et al., 2021). A study by Handayani et al. (2023) also found a significant
negative correlation between HbA1c and HDL-C (r=-0.377; p=0.026). The strength
of the correlation is relatively low, as other factors such as lifestyle and
diet can also affect HDL-C levels (Gordon, 1998).
The decrease in HDL-C in type 2 DM patients is also associated
with hypertriglyceridemia and obesity. The hypertriglyceridemia condition
activates CETP (cholesteryl ester transfer protein), which facilitates the
transfer of cholesterol esters (CE) from HDL-C to triglyceride-rich
lipoproteins (TGR-LPs), resulting in HDL-C that is poor in cholesterol esters
but rich in triglycerides. This form of HDL-C is more easily catabolized,
leading to a decrease in serum HDL-C levels (Verg�s, 2015) (Susilo et al., 2020) (Kostapanos & Elisaf, 2014) (Barter, 2011).
The consequences of decreased HDL-C in type 2 DM patients are associated
with a reduction in cardiovascular protection (Barter, 2011). One consequence is arterial stiffness, which leads to
atherogenic effects (Verg�s, 2015). Recent studies suggest that HDL-C has the ability to enhance
glucose uptake by skeletal muscle and stimulate insulin secretion from
pancreatic beta cells, so low HDL-C levels in type 2 DM may also contribute to
worsening diabetes control. Studies have shown that for every 1 mg/dL decrease
in HDL-C, the risk of coronary heart disease increases by 2% in men and 3% in
women (Kostapanos & Elisaf, 2014) (Barter, 2011).
Glycemic control indirectly affects the lipid profile. Lipid
profiles such as total cholesterol, triglycerides, and LDL-C will significantly
increase in type 2 DM patients with �poor glycemic control. HbA1c is
not only used as a long-term biomarker for glycemic control but also as a
predictor of lipid profile. Therefore, monitoring glycemic control using HbA1c
is useful for identifying the status of diabetic patients regarding
cardiovascular complications risk (Susilo et al., 2020).
Conclusion
The conclusion of this study is that there is a positive
correlation between glycemic control (HbA1c) and total cholesterol,
triglycerides, and LDL-C. There is a negative correlation between glycemic
control (HbA1c) and HDL-C. Significantly lower levels of total cholesterol,
triglycerides, and LDL-C were found in type 2 DM patients with good glycemic
control. Significantly higher levels of HDL-C were found in type 2 DM patients
with good glycemic control.
Based on this research, several recommendations are provided by
the researchers for future studies. In this study, not all confounding
variables were well-controlled, so the researchers recommend stricter control
over other confounding variables. Future studies could use cohort study methods
to explain the causal relationships between variables. The researchers also
suggest increasing the sample size so that the study sample is sufficiently
representative of the general population.
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