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Jurnal Info Kesehatan

Vol. 21, No. 2, June 2023, pp. 184-191
P-ISSN 0216-504X, E-ISSN 2620-536X
DOI: 10.31965/infokes.Vol21Iss2.933
Journal homepage:http://jurnal.poltekeskupang.ac.id/index.php/infokes
RESEARCH Open Access

Immunological Profile of Patients with Controlled and Uncontrolled Type 2

Diabetes Melitus in Mataram City, West Nusa Tenggara
I Putu Dedy Arjita1a*, I Gede Angga Adnyana1b, Ayu Anulus1c, I Putu Bayu Agus Saputra1d
Maruni Wiwin Diarti1e
1
Department of Herbal Medicine and Nutrigenomic, Faculty of Medicine, Universitas Islam Al-
Azhar Mataram, West Nusa Tenggara, Indonesia
2
Department of Medical Laboratory Technology, Poltekkes Kemenkes Mataram, Mataram, West
Nusa Tenggara, Indonesia
a
Email address: [email protected]
b
Email address: [email protected]
c
Email address: anulusayu @gmail.com
d
Email address: [email protected]
e
Email address: [email protected]
Received: 7 October 2022 Revised: 31 March 2023 Accepted: 31 March 2023
Abstract
The prevalence of DM disease in West Nusa Tenggara Province is not much different from that
in Indonesia. DM cases in NTB are included in the ten most non-communicable illnesses suffered
by the community and the incidence continues to increase from year to year. An increase in the
levels of pro-inflammatory cytokines in the body is one of the causes of insulin resistance in cells
which can further develop into type 2 diabetes. This study involved diabetic patients at the
Mataram Community Health Center, who were assigned into 2 groups, namely the controlled
diabetes group and the uncontrolled diabetes group and involved a standard group which was a
group consisted of healthy people. Each group was examined for Fasting Blood Glucose (FBG)
and HbA1c levels. The results of the examination in the standard group, controlled diabetes group
and uncontrolled diabetes group obtained the FBG levels of 89.22 mg/dl, 110.0 mg/dl, and 245.80
mg/dl, respectively. Furthermore, the results of the HbA1c test in the standard group, controlled
diabetes group and uncontrolled diabetes group were 5.44%, 6.03%, and 10.49%, respectively.
The results of the examination of IL-6 levels in the standard group, controlled diabetes group and
uncontrolled diabetes were 329.36 pg/ml, 331.52 pg/ml, and 320.33 pg/ml, respectively. The
results of the IL-10 test in the standard group, controlled diabetes group and uncontrolled diabetes
were 71.80 pg/ml, 116.60 pg/ml, and 128.10 pg/ml, respectively. Based on the results of the study,
there was no significant difference in the levels of interleukin 6 and interleukin 10 between
respondents with diabetes mellitus and healthy respondents (p>0.05). It can be concluded that
there were no differences in interleukin 6 and 10 levels between healthy people with patients with
controlled and uncontrolled diabetes.
Keywords: Diabetes mellitus, Pro-inflammatory, Interleukin, Glucose, HbA1c, Haemoglobin.

*Corresponding Author:
I Putu Dedy Arjita
Department of Herbal Medicine and Nutrigenomic, Faculty of Medicine, Universitas Islam Al-Azhar Mataram, West Nusa
Tenggara, Indonesia
Email: [email protected]
©The Author(s) 2023. This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution,
and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons
Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made
available in this article, unless otherwise stated.
Arjita, I. P. D., Adnyana, I. G. A., Anulus, A., Saputra, I. P. B. A. & Diarti, M. W. (2023). Immunological Profile of
Patients with Controlled and Uncontrolled Type 2 Diabetes Melitus in Mataram City, West Nusa Tenggara.
JURNAL INFO KESEHATAN, 21(2), 184-191. https://doi.org/10.31965/infokes.Vol21Iss2.933
| 185
1. INTRODUCTION
Currently, there are many significant changes in style and pattern of life of all people
around the world (Sheng et al., 2019). Lifestyle changes are not for the better, and even in a
negative direction, such as frequent consumption of fast food (Junk Food) and lack of
activity/exercise (sedentary)(Giri et al., 2020; Sheng et al., 2019). Such changes has led to an
increase in the incidence of non-communicable diseases in Indonesia, such as hypertension and
diabetes mellitus (DM)(Asril et al., 2020).
In Indonesia, the prevalence of DM sufferers continues to increase (Khan et al., 2020).
This can be observed in Basic Health Research data regarding DMin 2007, 2013, and 2018
which showed an increasing trend (Pradono et al., 2021). In 2019, cases of type 2 DM (Non-
Insulin Dependent Diabetes Mellitus) became the ten most common diseases in outpatient hajj
pilgrims in 2019 with a total of 15,679 patients (Yezli et al., 2021).
The prevalence of DM disease in West Nusa Tenggara Province is not much different
from that in Indonesia. DM cases in NTB are included in the ten most non-communicable
illnesses suffered by the community and the incidence continues to increase from year to year
(Annisa, Puspitasari, & Aini, 2021). In 2018, there were 33,828 DM cases recorded at the CHC,
which grew to 41,841 points in 2019. Even in 2019, metabolic diseases, such as DM, both type
1 and type 2, became the cause of death among pregnant women in NTB, as many as 12 cases.
In addition, according to data derived from the Indonesian Ministry of Health, in 2019, only
7.79% of patients with DM received standardized health services (Primayanto, 2022)
Type 2 Diabetes Mellitus (type 2 DM) is a metabolic disease caused by the body's failure
to process signals from the insulin hormone released by the pancreas (insulin resistance)
(Sacerdote et al., 2019). This failure can be due to various factors, including damage or failure
of the insulin signaling mechanism in cells (Zamora & Villena, 2019). This failure usually
involves Glucose Transporter-4 (GLUT4) and Insulin Receptor Substrate (IRS) in cells (Babu
et al., 2020). Such condition may further cause an increase in glucose levels outside the cell
since the glucose transport process from outside the cell into the cell cannot take place
(Poznyak et al., 2020).
An increase in the levels of pro-inflammatory cytokines in the body is one of the causes
of insulin resistance in cells which can further develop into type 2 diabetes (Akash, Rehman,
& Liaqat, 2018). An increase in the levels of pro-inflammatory cytokines among patients with
type 2 diabetes can be due to obesity (Wang & He, 2018). Various studies found the correlation
between an increase in the levels of pro-inflammatory cytokines such as TNF-alpha and IL-6
and obesity (Grosick, Alvarado-Vazquez, Messersmith, & Romero-Sandoval, 2018).
In addition to causing insulin resistance through cell signaling mechanisms, obesity also
causes an imbalance between the levels of pro-inflammatory cytokines and anti-inflammatory
cytokines (Guo et al., 2020). The increase in the levels of such pro-inflammatory cytokines
cause a person to experience a state of low-grade chronic inflammation which can further lead
to various complications and the emergence of other metabolic diseases, such as heart disease
and hypertension (Villarroya, et al., 2018). In addition, chronic inflammation that occurs
continuously and uncontrollably can increase susceptibility of a person to infection (Castro,
Macedo-de La Concha, & Pantoja-Meléndez, 2017; Ellulu et al., 2017).
There should be a balance between the levels of pro-inflammatory and anti-inflammatory
cytokines to minimize the risk and prevent disease complications related to metabolism.
Moreover, mapping of the immunological profile is also required (Bolte et al., 2021). Data on
anti-inflammatory and pro-inflammatory cytokine levels are required to get a clearer
description of the patient's immunological state. Therefore, researchers are interested in
conducting a study on the immunological profile of patients with controlled and uncontrolled
type 2 DM patients.
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2. RESEARCH METHOD
This was an analytic observational study with a cross-sectional approach. The population
in this study were all type 2 DM patients in the Mataram City Community Health Center.
Diabetic patients verified by the CHC were initially tested for the levels of fasting blood
glucose (FBG) and HbA1c to determine whether they had controlled and uncontrolled diabetes
mellitus.
The study samples involved healthy respondents and diabetic patients at the Mataram
CHC. There were 50 people as the sample population in this study. Respondents were assigned
into three groups: the control group (K) of healthy respondents and two observation groups
consisted of type 2 DM patients: the controlled type 2 DM (DT) group and the uncontrolled
type 2 DM patients (Figure 2). All respondents were examined for the levels of IL-6 and IL-
10. Distribution of the study samples is presented in the chart below.

Controlled type 2 DM

Population Sample DM Patients

Observation Group
Uncontrolled type 2 DM
Control Group (K)
Healthy People

Figure 1. Distribution flow of the study samples. There were 17 respondents with Controlled
type 2 DM, 17 respondents with uncontrolled type 2 DM, and 16 healthy respondents.
The inclusion criteria of the study samples involved here were adult male or female
patients with age range from 25-60 years, Diabetes mellitus patients who had been diagnosed
by a hospital or health care facility, were willing to become respondents, as evidenced by filling
out and signing the Informed Consent form, did not have a history of allergies and other
immunological diseases such as autoimmune and RA (rheumatoid arthritis), and had no
infectious disease either chronic or acute. This study has been approved by the Health Research
Ethics Committee, Faculty of Medicine, Al-Azhar Islamic University, through the letter
Number 53/EC-03/FK-06/UNIZAR/X/2021.

3. RESULTS AND DISCUSSION

Data regarding laboratory examination in each group of respondents are presented in
Table 1. Group assignment for controlled and uncontrolled diabetes was based on the results
of FBG and HbA1c levels assessment among respondents with type 2 diabetes mellitus.
Table 1. The Results of Examination for FBG, HbA1c, IL-6, and IL-10 levels.
Controlled type 2 Uncontrolled p-value
Variable Standard
DM type 2 DM
FBG (mg/dl) 89.22 110.0 245.80 p <0.05
HbA1c (%) 5.44 6.03 10.49 p <0.05
IL-6 (pg/ml) 329.36 331.52 320.33 p>0.05
IL-10 (pg/ml) 71.80 116.60 128.10 p>0.05
Regarding fasting blood glucose (FBG) levels in each group of respondents, there was a
significant difference (p<0.05) between the standard respondent group and the Diabetes
Mellitus (DM) respondent group. The results of the FBG analysis showed that controlled DM
respondents (110.0 mg/dl) and uncontrolled DM respondents (245.80 mg/dl) had different
levels of FBG which tended to be higher than average respondents.
Arjita, I. P. D., Adnyana, I. G. A., Anulus, A., Saputra, I. P. B. A. & Diarti, M. W. (2023). Immunological Profile of
Patients with Controlled and Uncontrolled Type 2 Diabetes Melitus in Mataram City, West Nusa Tenggara.
JURNAL INFO KESEHATAN, 21(2), 184-191. https://doi.org/10.31965/infokes.Vol21Iss2.933
| 187
Diabetes mellitus is a disease of glucose metabolism disorder characterized by an
increase in the levels of glucose in the blood (Xu et al., 2020). The results in this study indicated
differences in blood glucose levels between the groups of respondents. Such finding is in line
with a study conducted by Amir, Wungouw, and Pangemanan, (2015), which revealed that
there were high blood glucose levels among respondents with diabetes mellitus ( Amir,
Wungouw, & Pangemanan, 2015).
Regarding HbA1c levels, the study results showed a significant difference (p<0.05)
between the standard respondent group (5.44%) and the uncontrolled DM respondent group
(10.49%). Such finding indicated that the HbA1c levels could be a parameter to define the
uncontrolled DM group (Sherwani et al., 2016). However, there was no significant difference
between the standard respondent group and the controlled diabetes mellitus group. The HbA1c
examination is a specific examination to determine high blood glucose levels in the last two to
three months (Dağ et al., 2009). This examination can assess the risk of tissue damage caused
by high blood glucose levels in the blood (Utomo, Wungouw, & Marunduh, 2015).

Figure 2. Formation of binding of Hemoglobin Glucose

Glycated haemoglobin (HbA1c) is a monitoring parameter for diabetes which is

principally related to the half-life of red blood cells (RBC) (Sherwani et al., 2016).
Haemoglobin is a blood component that binds oxygen (Ahmed, Ghatge, & Safo, 2020). The
binding mechanism of haemoglobin to glucose can be observed in Figure 2. Haemoglobin will
bind glucose non-enzymatically at the N-terminal end of the beta chain of hemoglobin to
produce Schiff base aldimine. During the re-arrangement of Amadori, it will become a more
stable ketoamine product, namely HbA1c (Muralidharan, Bhat, & Mandal, 2020).
The results of the examination which showed high HbA1c levels in the uncontrolled
diabetes respondent group can be due to high blood glucose levels which facilitates the binding
to hemoglobin so that it can be used to see a history of high blood glucose levels in the last
three months (Silverman et al., 2006). The higher the blood glucose level, the more likely it is
to bind to hemoglobin in the blood (Gupta, Jain, & Chauhan, 2017). However, in respondents
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with controlled diabetes mellitus, HbA1c levels were not different from average respondents.
This could be due to a low-glucose diet to prevent an increase in blood glucose in the blood so
that there is no binding of blood glucose to hemoglobin (Paputungan & Sanusi, 2014).
Based on the results of the ANOVA test, there was a no significant difference in the mean
level of interleukin 10 between the standard respondent group (71.80 pg/ml) and the controlled
DM respondent group (116.60 pg/ml). In addition, there was no significant difference (p>0.05)
between the standard respondent group when compared to the uncontrolled DM group (128.10
pg/ml).
Interleukin 10 (IL-10) is an interleukin that plays a role in the anti-inflammatory
response. IL-10 is produced by immune cells (Treg, Th1, Th2, Th17, Macrophages, DC) in
response to inflammation, including IL-6 (Saraiva & O'garra, 2010). IL-10 is a cytokine widely
secreted by monocytes, which has a pleiotropic effect on the immune system and inflammation.
IL-10 was first recognized for its ability to inhibit activation and effector function of T cells,
monocytes, and macrophages (Sabat et al., 2010).
Based on the results of the ANOVA test, there was no significant difference in interleukin
6 (IL-6) levels (p>0.05) between average respondents (329.36 pg/ml), controlled DM
respondents (331.52 pg/ml), and uncontrolled DM respondents (320.33 pg/ml). IL-6 is
produced by adipose cells (adipokines) in response to the polarization of M2 to M1
macrophages among people with obesity (Matsubara et al., 2012; Trayhurn & Wood, 2005). In
addition, there is an increase in FFA levels which can activate TLR 4 in adipocytes and produce
an inflammatory response (Dasu et al., 2010; Hong et al., 2020).
In this study, there were no significant differences between the standard respondent group
with controlled diabetes, and uncontrolled diabetes. Such finding could occur because IL-6
and IL-10 produced from high glucose levels were still able to be suppressed by endogenous
and exogenous antioxidants presented in the patient's body so that no increase in IL-6 and IL10
was found (Wang et al., 2020). Diabetes mellitus can cause an increase in the production of
free radicals and generate reactive oxygen species (ROS) (Volpe et al., 2018). The increase in
free radicals can induce NF-KB to increase Interleukin 6 (Yeo et al., 2018). Reactive oxygen
species (ROS) should be reduced so that it cannot generate NF-Kb, and prevent the increase of
interleukin 6 (Kida et al., 2021).
In this study, the serum lipid levels were not assessed. Therefore, the relationship
between lipid levels and IL-6 could not be revealed. In a survey, it was also found that IL-10
levels were also inversely related to TG and LDL-C levels (Forero et al., 2018; Yuan et al.,
2018). Another study also found that in cases of insulin resistance and long-standing incidence
of type 2 diabetes, a slight increase in FFA levels was found (Den Hartogh et al., 2020). This
was thought to be related to the length of time respondents had suffered from DM, most of
which were more than one year.

4. CONCLUSION
High blood glucose can interfere with cell signaling and the immune response of the
human body. Still, in our study, there was no significant difference in the interleukin 6 and
interleukin 10 levels between respondents with diabetes mellitus and healthy respondents.
Elevated blood glucose levels may cause comorbidities that can be harmful to the body.
However, the effect of endogenous and exogenous antioxidants consumed by patients with
diabetes mellitus can play an important role in preventing the increase in IL-6 and IL-10 levels.
Arjita, I. P. D., Adnyana, I. G. A., Anulus, A., Saputra, I. P. B. A. & Diarti, M. W. (2023). Immunological Profile of
Patients with Controlled and Uncontrolled Type 2 Diabetes Melitus in Mataram City, West Nusa Tenggara.
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REFERENCES
Ahmed, M. H., Ghatge, M. S., & Safo, M. K. (2020). Hemoglobin: structure, function and
allostery. Vertebrate and invertebrate respiratory proteins, lipoproteins and other body
fluid proteins, 94, 345-382. https://doi.org/10.1007/978-3-030-41769-7_14
Akash, M. S. H., Rehman, K., & Liaqat, A. (2018). Tumor necrosis factor‐alpha: role in
development of insulin resistance and pathogenesis of type 2 diabetes mellitus. Journal
of cellular biochemistry, 119(1), 105-110. https://doi.org/10.1002/jcb.26174
Amir, S. M., Wungouw, H., & Pangemanan, D. (2015). Kadar glukosa darah sewaktu pada
pasien diabetes melitus tipe 2 di Puskesmas Bahu kota Manado. e-Biomedik, 3(1), 32-40.
Retrieved from https://ejournal.unsrat.ac.id/index.php/ebiomedik/article/view/6505
Annisa, B. S., Puspitasari, C. E., & Aini, S. R. J. S. J. P. (2021). Profil penggunaan obat
antidiabetes pada pasien diabetes mellitus tipe 2 di instalasi rawat jalan RSUD Provinsi
NTB tahun 2018. 2(1), 37-41. https://doi.org/10.29303/sjp.v2i1.74
Asril, N. M., Tabuchi, K., Tsunematsu, M., Kobayashi, T., Kakehashi, M. J. C. M. I. E., &
Diabetes. (2020). Predicting healthy lifestyle behaviours among patients with type 2
diabetes in rural bali, Indonesia. 13, 1179551420915856.
https://doi.org/10.1177/1179551420915856
Babu, S., Krishnan, M., Rajagopal, P., Periyasamy, V., Veeraraghavan, V., Govindan, R., &
Jayaraman, S. J. E. J. o. P. (2020). Beta-sitosterol attenuates insulin resistance in adipose
tissue via IRS-1/Akt mediated insulin signaling in high fat diet and sucrose induced type-
2 diabetic rats. 873, 173004. https://doi.org/10.1016/j.ejphar.2020.173004
Bolte, L. A., Vila, A. V., Imhann, F., Collij, V., Gacesa, R., Peters, V., . . . Fu, J. (2021). Long-
term dietary patterns are associated with pro-inflammatory and anti-inflammatory
features of the gut microbiome. Gut, 70(7), 1287-1298. http://dx.doi.org/10.1136/gutjnl-
2020-322670
Castro, A., Macedo-de La Concha, L., & Pantoja-Meléndez, C. (2017). Low-grade
inflammation and its relation to obesity and chronic degenerative diseases. Revista
Médica del Hospital General de México, 80(2), 101-105.
https://doi.org/10.1016/j.hgmx.2016.06.011
Dağ, A., Fırat, E., Arıkan, Ş., Kadiroğlu, A., & Kaplan, A. (2009). The effect of periodontal
therapy on serum TNF‐α and HbA1c levels in type 2 diabetic patients. Australian dental
journal, 54(1), 17-22. https://doi.org/10.1111/j.1834-7819.2008.01083.x
Dasu, M. R., Devaraj, S., Park, S., & Jialal, I. (2010). Increased toll-like receptor (TLR)
activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes care,
33(4), 861-868. https://doi.org/10.2337/dc09-1799
Den Hartogh, D. J., Vlavcheski, F., Giacca, A., & Tsiani, E. J. I. J. o. M. S. (2020). Attenuation
of free fatty acid (FFA)-induced skeletal muscle cell insulin resistance by resveratrol is
linked to activation of AMPK and inhibition of mTOR and p70 S6K. 21(14), 4900.
https://doi.org/10.3390/ijms21144900
Ellulu, M. S., Patimah, I., Khaza’ai, H., Rahmat, A., & Abed, Y. (2017). Obesity and
inflammation: the linking mechanism and the complications. Archives of medical
science, 13(4), 851-863. https://doi.org/10.5114/aoms.2016.58928
Forero, R., Nahidi, S., De Costa, J., Mohsin, M., Fitzgerald, G., Gibson, N., . . . Aboagye-Sarfo,
P. J. B. h. s. r. (2018). Application of four-dimension criteria to assess rigour of
qualitative research in emergency medicine. 18(120), 1-11.
https://doi.org/10.1186/s12913-018-2915-2
Giri, A. B., Shinde, V. T., Lengare, P. R., Shinde, R. D. J. G. B., & Sciences, P. (2020).
Lifestyle modifications: A key to manage diabetes. 13(3), 141-148.
https://doi.org/10.30574/gscbps.2020.13.3.0405
190 | https://doi.org/10.31965/infokes.Vol21Iss2.933

Grosick, R., Alvarado-Vazquez, P. A., Messersmith, A. R., & Romero-Sandoval, E. A. (2018).

High glucose induces a priming effect in macrophages and exacerbates the production of
pro-inflammatory cytokines after a challenge. Journal of pain research, 11, 1769.
https://doi:10.2147/JPR.S164493
Guo, X., Cheng, L., Yang, S., & Che, H. (2020). Pro-inflammatory immunological effects of
adipose tissue and risk of food allergy in obesity: Focus on immunological mechanisms.
Allergologia et immunopathologia, 48(3), 306-312.
https://doi.org/10.1016/j.aller.2019.06.004
Gupta, S., Jain, U., & Chauhan, N. (2017). Laboratory diagnosis of HbA1c: a review. J
Nanomed Res, 5(4), 00120. http://doi.org/10.15406/jnmr.2017.05.00120
Hong, Y.-p., Yu, J., Su, Y.-r., Mei, F.-c., Li, M., Zhao, K.-l., . . . Wang, W.-x. (2020). High-fat
diet aggravates acute pancreatitis via TLR4-mediated necroptosis and inflammation in
rats. Oxidative Medicine and Cellular Longevity, 2020(8172714).
https://doi.org/10.1155/2020/8172714
Khan, M. A. B., Hashim, M. J., King, J. K., Govender, R. D., Mustafa, H., Al Kaabi, J. J. J. o.
e., & health, g. (2020). Epidemiology of type 2 diabetes–global burden of disease and
forecasted trends. 10(1), 107. https://doi.org/10.2991/jegh.k.191028.001
Kida, T., Oku, H., Osuka, S., Horie, T., & Ikeda, T. (2021). Hyperglycemia-induced VEGF
and ROS production in retinal cells is inhibited by the mTOR inhibitor, rapamycin.
Scientific reports, 11(1885). https://doi.org/10.1038/s41598-021-81482-3
Matsubara, T., Mita, A., Minami, K., Hosooka, T., Kitazawa, S., Takahashi, K., . . . Matsuo,
E.-i. (2012). PGRN is a key adipokine mediating high fat diet-induced insulin resistance
and obesity through IL-6 in adipose tissue. Cell metabolism, 15(1), 38-50.
https://doi.org/10.1016/j.cmet.2011.12.002
Muralidharan, M., Bhat, V., & Mandal, A. K. (2020). Structural analysis of glycated human
hemoglobin using native mass spectrometry. The FEBS Journal, 287(6), 1247-1254.
https://doi.org/10.1111/febs.15085
Paputungan, S. R., & Sanusi, H. (2014). Peranan Pemeriksaan Hemoglobin A1c pada
Pengelolaan Diabetes Melitus. Cermin Dunia Kedokteran, 41(9), 650-655.
http://dx.doi.org/10.55175/cdk.v41i9.1103
Poznyak, A., Grechko, A. V., Poggio, P., Myasoedova, V. A., Alfieri, V., & Orekhov, A. N. J.
I. j. o. m. s. (2020). The diabetes mellitus–atherosclerosis connection: The role of lipid
and glucose metabolism and chronic inflammation. 21(5), 1835.
https://doi.org/10.3390/ijms21051835
Pradono, J., Delima, D., Kusumawardani, N., Dany, F., & Kristanto, Y. J. G. J. o. H. S. (2021).
Contribution of Metabolic Syndrome in Controlling Diabetes Mellitus According to
Gender in Indonesia (RISKESDAS 2018). 13(1), 1-46.
https://doi.org/10.5539/gjhs.v13n1p46
Primayanti, I., Danianto, A., Jumsa, R., Geriputri, N., & Andari, M. Y. J. J. K. (2022).
Gambaran Epidemiologi Faktor Risiko Preeklamsia Pada Ibu Hamil. 11(1), 785-788.
https://doi.org/10.29303/jku.v11i1.624
Sabat, R., Grütz, G., Warszawska, K., Kirsch, S., Witte, E., Wolk, K., & Geginat, J. (2010).
Biology of interleukin-10. Cytokine & growth factor reviews, 21(5), 331-344.
http://dx.doi.org/10.1016/j.cytogfr.2010.09.002
Sacerdote, A., Dave, P., Lokshin, V., & Bahtiyar, G. J. C. d. r. (2019). Type 2 diabetes mellitus,
insulin resistance, and vitamin D. 19(10), 1-12. https://doi.org/10.1007/s11892-019-
1201-y
Saraiva, M., & O'garra, A. (2010). The regulation of IL-10 production by immune cells. Nature
reviews immunology, 10, 170-181. http://dx.doi.org/10.1038/nri2711
Arjita, I. P. D., Adnyana, I. G. A., Anulus, A., Saputra, I. P. B. A. & Diarti, M. W. (2023). Immunological Profile of
Patients with Controlled and Uncontrolled Type 2 Diabetes Melitus in Mataram City, West Nusa Tenggara.
JURNAL INFO KESEHATAN, 21(2), 184-191. https://doi.org/10.31965/infokes.Vol21Iss2.933
| 191
Sheng, Z., Cao, J.-Y., Pang, Y.-C., Xu, H.-C., Chen, J.-W., Yuan, J.-H., . . . Dong, J. J. F. i. e.
(2019). Effects of lifestyle modification and anti-diabetic medicine on prediabetes
progress: A systematic review and meta-analysis. 10, 455.
https://doi.org/10.3389/fendo.2019.00455
Sherwani, S. I., Khan, H. A., Ekhzaimy, A., Masood, A., & Sakharkar, M. K. (2016).
Significance of HbA1c test in diagnosis and prognosis of diabetic patients. Biomarker
insights, 11, BMI. S38440. https://doi.org/10.4137/BMI.S38440
Silverman, R. A., Pahk, R., Carbone, M., Wells, E., Mitzner, R., Burris, K., . . . Katzeff, H.
(2006). The relationship of plasma glucose and HbA1c Levels among emergency
department patients with no prior history of diabetes mellitus. Academic emergency
medicine, 13(7), 722-726. https://doi.org/10.1197/j.aem.2006.02.012
Trayhurn, P., & Wood, I. (2005). Signalling role of adipose tissue: adipokines and
inflammation in obesity. Biochemical Society Transactions, 33(5), 1078-1081.
https://doi.org/10.1042/BST0331078
Utomo, M. R., Wungouw, H., & Marunduh, S. (2015). Kadar Hba1C Pada Pasien Diabetes
Melitus Tipe 2 Di Puskesmas Bahu Kecamatan Malalayang Kota Manado. eBiomedik,
3(1). Retrieved from https://ejournal.unsrat.ac.id/index.php/ebiomedik/article/view/6620
Villarroya, F., Cereijo, R., Gavaldà‐Navarro, A., Villarroya, J., & Giralt, M. (2018).
Inflammation of brown/beige adipose tissues in obesity and metabolic disease. Journal
of internal medicine, 284(5), 492-504. https://doi.org/10.1111/joim.12803
Volpe, C. M. O., Villar-Delfino, P. H., Dos Anjos, P. M. F., Nogueira-Machado, J. A. J. C. d.,
& disease. (2018). Cellular death, reactive oxygen species (ROS) and diabetic
complications. 9(2), 1-9. https://doi.org/10.1038/s41419-017-0135-z
Wang, T., & He, C. (2018). Pro-inflammatory cytokines: The link between obesity and
osteoarthritis. Cytokine & growth factor reviews, 44, 38-50.
https://doi.org/10.1016/j.cytogfr.2018.10.002
Wang, Z., Wang, Z., Huang, W., Suo, J., Chen, X., Ding, K., . . . Zhang, H. (2020). Antioxidant
and anti-inflammatory activities of an anti-diabetic polysaccharide extracted from
Gynostemma pentaphyllum herb. International journal of biological macromolecules,
145, 484-491. https://doi.org/10.1016/j.ijbiomac.2019.12.213
Xu, L.-N., Yin, L.-H., Jin, Y., Qi, Y., Han, X., Xu, Y.-W., . . . Peng, J.-Y. (2020). Effect and
possible mechanisms of dioscin on ameliorating metabolic glycolipid metabolic disorder
in type-2-diabetes. Phytomedicine, 67, 153139.
https://doi.org/10.1016/j.phymed.2019.153139
Yeo, D., Hwang, S. J., Kim, W. J., Youn, H.-J., Lee, H.-J. J. B., & Pharmacotherapy. (2018).
The aqueous extract from Artemisia capillaris inhibits acute gastric mucosal injury by
inhibition of ROS and NF-kB. 99, 681-687. https://doi.org/10.1016/j.biopha.2018.01.118
Yezli, S., Mushi, A., Almuzaini, Y., Balkhi, B., Yassin, Y., Khan, A. J. I. J. o. E. R., & Health,
P. (2021). Prevalence of diabetes and hypertension among Hajj pilgrims: a systematic
review. 18(3), 1155. https://doi.org/10.3390/ijerph18031155
Yuan, N., Zhang, H.-f., Wei, Q., Wang, P., Guo, W.-y. J. E., Endocrinology, C., & Diabetes.
(2018). Expression of CD4+ CD25+ Foxp3+ regulatory T cells, interleukin 10 and
transforming growth factor β in newly diagnosed type 2 diabetic patients. 126(02), 96-
101. https://doi.org/10.1055/s-0043-113454
Zamora, M., & Villena, J. A. J. I. j. o. m. s. (2019). Contribution of impaired insulin signaling
to the pathogenesis of diabetic cardiomyopathy. 20(11), 2833.
https://doi.org/10.3390/ijms20112833