p ISSN
2723-6927-e ISSN 2723-4339
The Relationship Between Glycemic Control And Lipid Profile In
Patients With Type 2 Diabetes Mellitus
In Bangli Hospital
Made AA Pradnyani1*, I Ketut Sutarjana2
General Practitioner, Bangli Regional General Hospital, Bali,
Indonesia1*
Department of Internal Medicine, Bangli Regional General Hospital,
Bali, Indonesia2
Email: agustia322@gmail.com
ABSTRACT
Diabetes Mellitus
(DM) tipe 2 rentan terhadap dislipidemia diabetik, yang meningkatkan risiko komplikasi penyakit
kardiovaskular. Penelitian ini bertujuan untuk menentukan hubungan antara
pengendalian glikemik dan profil lipid pada pasien DM tipe 2. Studi cross-sectional dilakukan di Poliklinik Penyakit Dalam RSUD
Bangli dari Januari hingga Desember 2023, melibatkan 60 pasien DM tipe 2 yang
memenuhi kriteria inklusi. Pasien dikelompokkan menjadi dua, yaitu dengan
kontrol glikemik baik (HbA1c < 7%) dan kontrol glikemik buruk (HbA1c ≥
7%). Pada pasien dengan kontrol glikemik baik, kadar kolesterol total lebih
rendah (160,444 ± 30,608 mg/dl vs 203,476 ± 45,471 mg/dl; p= 0.001), trigliserida (125,500 ± 56,019 vs 202,047
± 91,568; p= 0.002), dan low-density lipoprotein
(K-LDL) (93,072 ± 28,443 vs 131,571 ± 44,590; p= 0.001). Kadar high-density lipoprotein (K-HDL) juga lebih tinggi (50,022
± 14,050 vs 41,152 ± 12,619; p = 0.019) pada pasien dengan kontrol glikemik
baik. Uji statistik menunjukkan korelasi positif antara kadar kolesterol total
(r = 0.277; p = 0.032), trigliserida (r = 0.386; p = 0.002), dan K-LDL (r =
0.357; p = 0.005) dengan kadar HbA1c, serta korelasi negatif antara K-HDL
(r=-0.366; p = 0.004) dan HbA1c. Korelasi signifikan ini menegaskan pentingnya
pengendalian glikemik pada pasien DM tipe 2.
Keywords: Diabetes Mellitus, Cholesterol,
K-HDL, K-LDL, Triglycerides
INTRODUCTION
Diabetes mellitus (DM) is a group of
metabolic diseases characterized by hyperglycemia that occurs due to
abnormalities in insulin secretion, insulin action, or both (Salsabila & Sjaaf, 2022). DM is currently one of the chronic diseases with the highest
prevalence rate throughout the world (Voeltz, Tönnies, Brinks, &
Hoyer, 2022). According to research Epidemiologically, currently there are 387
million people suffering from DM worldwide, which is expected to increase to
592 million people in 2035 to 642 million people in 2040 (Zheng, Ley, & Hu, 2018).
HbA1c (glycated hemoglobin) is a type of hemoglobin that shows the
average concentration of plasma glucose in 3 months which has been recommended
by PERKENI as a long-term glucose evaluation in type
2 DM sufferers (Goyal, Singhal, & Jialal,
2023). High HbA1c is independently associated
with increased risk of macrovascular or microvascular complications and is associated with metabolic syndrome (Committee, 2011)(Indonesia, 2021). HbA1c is not only a sign of glycemic control but can also be
used as a predictor of dyslipidemia (Saepudin, Ball, & Morrissey,
2016).
Type 2 DM patients are susceptible to
diabetic dyslipidemia, namely abnormalities in lipid metabolism which is one of
the factors that contributes to an increased risk of complications from
cardiovascular disease. Diabetic dyslipidemia includes not only quantitative
but also qualitative lipoprotein abnormalities resulting in a shift towards an atherogenic lipid profile (Kumar et al., 2022)(Devhy & Widana, 2019). The hyperglycemia, insulin resistance and relative insulin
deficiency observed in Type 2 DM patients most likely contribute to lipid
changes, because insulin plays an important role in regulating
lipid metabolism (Reza, Dwi, Jihan, Kurnia, &
Afra, 2023).
From the various empirical evidence presented above, the
relationship between glycemic control and lipid profile needs to be studied
further. Evidence regarding the relationship between glycemic control and lipid
profile in patients with type 2 diabetes is currently conflicting. Because
there is still conflicting evidence regarding the relationship between glycemic
control and lipid profile, this research was carried out with the aim of
determining the relationship between glycemic control and lipid profile in type
2 DM patients at Bangli
Regional Hospital.
RESEARCH METHODS
This research is a correlational analytical study with
a cross sectional approach to determine the relationship between glycemic
control (HbA1c) with lipid profiles in type 2 DM
patients. The research was carried out at the Internal Medicine Polyclinic at
Bangli Regional Hospital periodJanuary 2023 –
December 2023. Data was taken from the patient's medical record.
Ethical approval was obtained from the Health Research
Ethics Committee of Bangli Regional Hospital (No.400.7.22.2/1024/RSUD) to
ensure that the research was carried out in accordance with procedures. Consent
was obtained from the subjects after explaining the details of the research in
Indonesian and/or regional languages (Balinese). Confidentiality is guaranteed in this research.
The target population isall outpatients
who have been diagnosed with type 2 DM, while the accessible population is type
2 DM sufferers at Bangli Regional Hospital, especially patientsInternal Medicine
Polyclinic ywho meet the inclusion and exclusion
criteria. Inclusion criteria: patients diagnosed with type 2 DM andthere
is data in the medical record in the form of HbA1c and lipid profile (total
cholesterol, K-HDL, K-LDL, triglycerides); Exclusion
criteria: Type 2 DM patients who do not havedata in medical records in
the form of HbA1c and lipid profile (total cholesterol, K-HDL, K-LDL,
triglycerides), type 2 DM patients with previous dyslipidemia therapy (statins,
fibrates, niacin), pregnant patients, patients who have thyroid disease,
chronic liver disease, chronic kidney disease and other endocrine disorders.
The minimum sample size required is 51 people.
The sampling technique in this research is
non-probability sampling, namely purposive sampling by determining inclusion
and exclusion criteria. From purposive sampling it was obtainedThe sample size of 60 people is what is required in this research.
Dependent variable: the dependent variable examined in this
research islipid profile in the form oftotal
cholesterol, triglycerides, K-LDL and K-HDL. The scale used is numerical.
Independent variable: the independent variable examined in this study is
glycemic control through HbA1c examination.HbA1C
levels will be grouped into 2 groups. Patients with HbA1c levels <7% were
categorized as a controlled glycemic control group, while patients
with HbA1c levelsHbA1c≥7%categorized as uncontrolled
glycemic control group. The scale used is numerical.
By operational definition, type 2 DM patients are patients who
have been diagnosed with type 2 DM at the Internal Medicine Polyclinic of
Bangli Regional Hospital for the period January 2023 to December 2023. Patient
assessments were obtained from the patient's medical records at the Internal
Medicine Polyclinic of Bangli Regional Hospital. Glycemic control assessment is
obtained from laboratory results of HbA1c, which is the average plasma glucose
level. Assessment of the lipid profile is assessed by total cholesterol levels,
triglycerides, K-LDL and K-HDL levels.
Statistical analysis was carried out by testing data
homogeneity followed by comparative tests and correlation tests. Comparative
tests between total cholesterol, triglyceride, K-LDL and K-HDL levels were
carried out in the controlled glycemic control group and the uncontrolled
glycemic control group. Comparative tests were carried out using the
independent T test. The correlation test assesses the relationship between
glycemic control (HbA1c) and total cholesterol, triglyceride, K-LDL and K-HDL
levels. The correlation test used is the Pearson correlation test, if the
patience data is normal, if the data patience data is not normal then an
alternative test is used, namely the Spearman correlation test. All tests were
considered significant if the p value < 0.05. Data analysis was carried out
with the help of SPSS version 26 software.
RESULTS AND DISCUSSION
In this study, of 60 type 2 DM patients, there were 18 patients in
the controlled glycemic control group and 42 patients in the uncontrolled
glycemic control group. There were 18 patients with controlled glycemic
control, 7 people (38.9%) were male and 11 people (61.1%) were female patients.
In the uncontrolled glycemic control group there were 42 people, 24 people
(57.1%) were men and 18 people (42.9%) were women. Judging from age
characteristics, it was found that the mean age of patients with controlled and
uncontrolled glycemic control was 66,277 years and 60,170 years respectively.
Patients with controlled glycemic control had an average HbA1c level of 5,991
and the average HbA1c in the group of patients with uncontrolled glycemic
control was 9,471. The characteristics of the respondents
can be seen
in Table 1.
Table 1. Characteristics of Respondents
|
Characteristics |
HbA1c |
||
|
Controlled Glycemic Control (<7%) n = 18 |
Uncontrolled Glycemic Control (≥7%) n = 42 |
p-value |
|
|
Gender, n (%) |
|
|
0.201 |
|
Man |
7 (38.9) |
24 (57.1) |
|
|
Woman |
11 (61.1) |
18 (42.9) |
|
|
Average Age |
66,277 |
60,170 |
0.043 |
|
Average HbA1c |
5,991 |
9.4710 |
0,000 |
Comparative analysis of the lipid profile of type 2 DM
patients between controlled glycemic control and uncontrolled glycemic control
was carried out using the independent T test. The results of this study showed
that the group of patients with controlled glycemic control had lower levels of
total cholesterol, triglycerides and K-LDL, while the group of patients with
controlled glycemic control had higher K-HDL. Differences in lipid profiles
based on glycemic control are presented in Table 2.
Table 2. Differences in
Lipid Profile Levels Based on Glycemic Control
|
HbA1c |
|||
|
Controlled Glycemic Control
(<7%) n = 18 |
Uncontrolled Glycemic Control (≥7%) n = 42 |
p-value |
|
|
Total cholesterol |
160,444 ± 30,608 |
203,476 ± 45,471 |
0.001 |
|
Ttriglycerides |
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 carrying out a correlation test between
glycemic control (HbA1c) and lipid profile, first carry out a normality test.
The normality test used was the Kolmogorov-Smirnov test because the number of
samples in the study was > 50. In the Kolmogorov-Smirnov test, data on HbA1c
(p=0.200), total cholesterol (p=0.200), K-LDL (p=0.200) were normally
distributed, while data on triglycerides (p=0.000) and K-HDL (p= 0.040) are not
normally distributed and
are presented in Table 3.
Table 3. Results of
Glycemic Control Normality Test
(HbA1c) and Lipid Prodil
|
Variable |
Sig. |
Information |
|
HbA1c |
0.200 |
Normal |
|
Total cholesterol |
0.200 |
Normal |
|
Triglycerides |
0,000 |
Abnormal |
|
K-LDL |
0.200 |
Normal |
|
K-HDL |
0.040 |
Abnormal |
Correlation test between glycemic control (HbA1c) and
lipid profile using the Pearson correlation test for normally distributed data
and the Spearman correlation test for abnormally distributed data, obtained a
weak positive correlation between HbA1c and total cholesterol, triglycerides
and K-LDL. A positive correlation indicates a unidirectional relationship, so
it can be concluded that the higher the HbA1c level, the higher the total
cholesterol, triglycerides and K-LDL will also be. There is a weak negative
correlation between glycemic control (HbA1c) and K-HDL. Negative correlation
indicates an opposite relationship, so it can be concluded that the higher the
HbA1c level, the lower the K-HDL. The results of the correlation test between
glycemic control (HbA1c) and lipid profile are presented in Table 4.
Table 4. Correlation Test
Results between Glycemic Control (HbA1c) and Lipid Profile
|
Connection |
Sig. |
Correlation coefficient |
|
HbA1c with Total Cholesterol |
0.032 |
0.277 |
|
HbA1c with K-LDL |
0.005 |
0.357 |
|
HbA1c with Triglycerides |
0.002 |
0.386 |
|
HbA1c with K-HDL |
0.004 |
-0.366 |
Discussion
Type 2 DM patients are susceptible to diabetic dyslipidemia,
namely abnormalities in lipid metabolism that not only include quantitative but
also qualitative lipoprotein abnormalities that result in a shift towards an
atherogenic lipid profile. Lipid abnormalities in type 2 DM are most likely the
result of hyperglycemia, insulin resistance and relative insulin deficiency
observed in type 2 DM patients. Dyslipidemia is a predictor
of cardiovascular disease (Reza et al., 2023).
In this study it was found that type 2 DM patients
with controlled glycemic control (HbA1c < 7%), had lower levels of total
cholesterol, triglycerides and K-LDL than type 2 DM patients with uncontrolled
glycemic control (HbA1c≥7%). This research is in line with that conducted by
Handayani et al (2023) which showed
that total cholesterol,
triglyceride and K-LDL levels were lower in the controlled glycemic group. The
results of this study are also in line with the results of research
by Reza (2023) and Made Junior et al (2019) with similar
findings.
Based on the results of the correlation test, 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 K-LDL (r = 0.357; p = 0.005). The strength of the correlation is low. This
pattern of relationship can be explained based on the consistency of results
with previous studies or an explanation using a pathophysiological theoretical
approach regarding the relationship between glycemic control and lipid profile.
The results of this study are consistent with research
conducted by Susilo et al (2020), in their research there was a significant relationship between the HbA1c value and total cholesterol levels in Type 2 DM sufferers (p=0.030; r= +0.314). (16) Similar research
results also shown by Nnakenyi (2022), in his research showed
that there was a positive relationship between HbA1c and total cholesterol (r =
0.406, p <0.05), triglycerides (r = 0.273, p <0.05), K-LDL (r= 0.409, p
< 0.05). Research conducted by Made Junior et al (2019) using 140 type 2 DM patients also showed a similar thing, namely that
there was a positive relationship between HbA1c and total cholesterol,
triglyceria, K-LDL ( r=0.472; r=0.276;r=0.679) .
Patients with Type 2 DM experience decreased plasma campesterol
levels (a marker of cholesterol absorption) and increased plasma latosterol
levels (a marker of cholesterol synthesis). This mechanism underlies changes in
cholesterol homeostasis. The expression of SREBP2 (which codes for sterol
regulation, a factor that regulates uptake and synthesis) is increased in type 2 DM patients (Vergès, 2015).
Hypertriglyceridemia is the most common serum lipid abnormality found in DM patients. The increase in plasma triglyceride levels in Type 2 DM patients is largely caused
by an increase
in the amount of VLDL, especially large VLDL1 (very low-density lipoprotein subfraction
1) particles and delays in VLDL catabolism causing an increase
in the VLDL pool. Decreased VLDL catabolism due to insulin resistance can cause a decrease in lipoprotein
lipase (LPL) activity, which
results in decreased chylomicron and VLDL catabolism, resulting in more severe hypertriglyceridemia.
Other mechanisms such as de novo
lipogenesis also contribute to increasing
plasma triglycerides in type
2 DM (Vergès, 2015).
In type 2 DM patients, K-LDL also increases. This is due to a
significant reduction in K-LDL catabolism which causes a longer duration of
K-LDL in plasma which can increase lipid deposition into the arterial wall.
Another mechanism is the result of a significant reduction in the number of
K-LDL B/E cell surface receptors and a decrease in the affinity of K-LDL to its
receptor due to ApoB glycation (K, Kunikullaya, & Goturu,
2014). Patients with
type 2 DM experience an increase in oxidized K-LDL in
plasma. Oxidized K-LDL is formed from triglycerides which are abundant in VLDL
and exchange with cholesterol esters (CE) from K-LDL in the circulation. This
will produce LDL that is rich in triglycerides but lacking cholesterol esters,
resulting in small dense LDL, known as small dense LDL. These small, dense LDL particles are highly atherogenic (Artha et al., 2019).
Then, based on the results of the correlation test
between glycemic control (HbA1c) and K-HDL (r=-0.366; p = 0.004), a significant
negative correlation was found. The strength of the correlation is low. Similar
results were also obtained from research by Huang et al (2021) using 3171 type 2 DM patients showing that there was a negative
relationship between HbA1c and K-HDL (p= 0.044).
Research by Handayani et al
(2023) also obtained
similar results, namely significant relationship between HbA1c and K-HDL and
negatively correlated (r=-0.377; p=0.026). The strength of the correlation is
low because there are still other factors that influence K-HDL such as lifestyle and diet.
Decreased K-HDL in type 2 DM patients is also associated with
hypertriglyceridemia and obesity. Hypertriglyceride conditions activate CETP
(cholesteryl ester transfer protein) encouraging the transfer of cholesterol
ester (CE) from K-HDL to triglyceride-rich lipoproteins (TGR-LPs) which results
in K-HDL being poor in cholesterol ester but rich in triglycerides. Then K-HDL
in this form is more easily catabolized so that the amount of
serum HDL decreases (Kostapanos & Elisaf, 2014).
The consequences of decreasing K-HDL in type 2 DM patients are
related to reduced cardiovascular protective
effects (Barter, 2011). One of the consequences is arterial stiffness which causes atherogenic
effects (Vergès, 2015). Recent studies show that K-HDL has the ability to increase
glucose absorption by skeletal muscle and stimulate insulin secretion from
pancreatic beta cells so that K-HDL concentrations are low in type 2 DM as
well. may contribute to worsening diabetes control. Studies show that for every
1 mg/dL reduction in K-HDL levels, the risk of CHD increases by 2% in men and 3% in women (Barter, 2011).
Glycemic control indirectly influences the lipid
profile. Lipid profiles such as total cholesterol, triglycerides, K-LDL will
increase significantly in type 2 DM patients with uncontrolled glycemic
control. HbA1c is not only used as a long-term biomarker for glycemic control,
but also as an appropriate predictor of lipid profile. Therefore, monitoring
glycemic control using HbA1c is useful for identifying the status of diabetes
mellitus patients regarding the risk of cardiovascular complications (Sulolipu, Handoyo,
& Roziqin, 2019).
CONCLUSION
The conclusion of this study is that there is a positive
correlation between glycemic control (HbA1c) and total cholesterol,
triglycerides and K-LDL. There is a negative correlation between glycemic
control (HbA1c) and K-HDL. Total cholesterol, triglyceride and K-LDL levels
were significantly lower in Type 2 DM patients with good glycemic control.
K-HDL levels were significantly higher in Type 2 DM patients with good glycemic
control. Based on this research,
there are several suggestions given by the researcher for further research,
such as in this study not all confounding variables can be controlled properly,
so the researcher suggests tighter control of other confounding variables.
Future research can use research methods such as cohorts so that they can
explain the causal relationship between variables.PResearchers also suggest increasing the sample size so that the
research sample is adequate to represent the general population.
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Copyright Holder: Made AA Pradnyani, I Ketut Sutarjana (2024) |
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