117

BIOMOLECULAR AND HEALTH SCIENCE JOURNAL 2019 OCTOBER, VOL 02 (02)

ORIGINAL ARTICLE

Relationship between HbA1c Levels with eGFR and

Blood Pressure in Type 2 Diabetes Mellitus Patients at
General Hospital in Surabaya

Alexander Tikara Sugondo1, Djohar Nuswantoro2, Paulus Budiono Notopuro3, Deasy

Ardiany4*
1
Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia
2
Department of Public Health and Preventive Medicine, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia - Dr.
Soetomo General Hospital Surabaya, Indonesia
3
Department of Internal Medicine, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia - Dr. Soetomo General
Hospital Surabaya, Indonesia
4
Department of Internal Medicine, Faculty of Medicine Universitas Airlangga, Surabaya, Indonesia - Dr. Soetomo General
Hospital Surabaya, Indonesia

ARTICLE INFO ABSTRACT

Article history: Introduction: Diabetes mellitus is ranked seventh as the cause of death in the world, around 95%
Received 22 August 2019 in the world is type 2 diabetes mellitus (T2DM). According to Riset Kesehatan Dasar (Riskesdas)
Received in revised form 14 in 2013, the prevalence of diabetes mellitus in Indonesia is 6.9%. Type 2 diabetes mellitus that is
October 2019 not well controlled will increase the risk of chronic complications, both microangiopathies such as
Accepted 29 October 2019 nephropathy, and macroangiopathy such as hypertension. The aim of the study was to determine
correlation between HbA1c levels with eGFR (Estimated Glomerulus Filtration Rate) and blood
pressure (systolic and diastolic).
Keywords: Methods: An analytic observational cross-sectional study, collecting the data from 94 patients with
Type 2 diabetes mellitus, T2DM,. The variables were collected from patient’s medical records. Analysis using Spearman’s
HbA1c, Rank Correlation test.
Blood pressure, Results: From total 232 patients, 134 (57.8%) were females, 203 (87.5%) >45 years old with
eGFR. average age 55.57. There was no significant correlation between HbA1c and systolic blood pressure
and there was no significant correlation between HbA1c and diastolic blood pressure.There was no
significant correlation between HbA1c and systolic blood pressure (r=-0.127; p=0.054). Also no
significant correlation between HbA1c and diastolic blood pressure (r=-0.111; p=0.093). Analysis
on other factor showed a significant correlation between HbA1c and eGFR (r=0.341; p=0.000).
Conclusion: No significant correlation between HbA1c and systolic blood pressure, and between
HbA1c and diastolic blood pressure. Significant correlation between HbA1c and eGFR.

Introduction genetic factors, and age could increase T2DM prevalence.

Diabetes mellitus is a global scale concern non- While people can work on modifiable risk factor that are
communicable disease.1 There are several types of diabetes related to physical condition and social life, Body Mass
mellitus, type 1, type 2, gestational type and other types Index (BMI), waist circumference, alcohol consumption,
of diabetes mellitus. T2DM is a disease with metabolic work and physical activity, education level, and smoking
disorders due to damage in insulin secretion or disorders habits.3
of pancreatic beta cells and / or impaired insulin function. T2DM that is un-controlled will increase the risk of
The prevalence of diabetes mellitus in the world according chronic complications, both microangiopathies such as
to the International Diabetes Federation (IDF) is 1.9% nephropathy, and macroangiopathy such as hypertension.4
and diabetes mellitus is ranked seventh as the cause of Theoretically, every person with type 2 diabetes mellitus is
death in the world, around 95% in the world is T2DM.2 at risk of experiencing chronic complications. It depends on
According to Riset Kesehatan Dasar (Riskesdas) in 2013, uncontrolled sugar levels, a history of hypertension, kidney
the prevalence of diabetes mellitus in Indonesia is 6.9%. damage, and long-standing diabetes mellitus. People with
Several unmodifiable risk factors, including gender, T2DM and hypertension will increase the risk of getting

*Correspondence: [email protected]
Biomolecular and Health Science Journal
Available at https://e-journal.unair.ac.id/BHSJ
DOI: 10.20473/bhsj.v2i2.14956
 BIOMOLECULAR AND HEALTH SCIENCE JOURNAL 2019 OCTOBER, VOL 02 (02) 118

coronary heart disease higher. In addition, poor control of diabetes mellitus in this study. According to Indonesian
diabetes mellitus, characterized by hyperglycemia, will Endocrinology Association, high risk groups are patients
progressively lead to a decrease in the Glomerular Filtration over the age of 45 years.12 The group > 45 years has a
Rate (GFR) and the destruction of the glomeruli, leading much higher number than the group ≤ 45 years. We found
to chronic kidney disease.5 In this study, uncontrolled more women than men in the group of subjects under the
diabetes mellitus seen from its HbA1c values. HbA1c is age of 45 years, as well as the other group.
the component of hemoglobin that binds to blood sugar. HbA1c values were found to be higher in women than
In cardiovascular complications, diabetes mellitus can men. The eGFR in men is slightly better than in women.
interfere with the function of diastole and systole. Patients Whereas the blood pressure did not get much difference.
with diabetes mellitus usually have diastolic dysfunction Data presented with mean and standard deviation (table 1).
before experiencing systolic dysfunction.6 Macrovascular
complications can be in the form of heart disease, stroke,
Table 1. Gender and age groups of people with type 2
and peripheral blood vessels where peripheral artery disease
diabetes mellitus
can cause wounds that are difficult to heal, gangrene,
and can even be amputated. Other complications cause a Characteristic Gender(mean±SD)
decrease in infection resistance, pneumonia, macrosomia, Male (n=98) Female (n=134)
and complications during childbirth.7 These complications Age groups (years)
lead to kidney failure, gangrene, vision problems,
and cardiovascular disorders such as arteriosclerosis, <45 13(39±4.42) 16(37.06±5.88)
myocardial infarction, stroke, and lower extremity artery ≥45 85(59.07±9.3) 118(57.38±7.2)
obstruction. Patients with uncontrolled blood sugar levels HbA1c (8.14±2.39) (8.28±2.56)
and have diabetes for a long time as mentioned above are
directly proportional to the incidence of microvascular eGFR (56.66±47.15) (54.78±47.66)
complications.5,8 Unfortunately, there have been few SBP (130.72±19.38) (130.72±18.88)
researches to evaluate diastolic dysfunction in patients DBP (80.78±10.24) (82.07±9.93)
with diabetes mellitus.9 In addition, the main complication
of patients with diabetes mellitus is diabetic nephropathy The data obtained is not normally distributed with α=0.05.
and is a major cause of terminal stage of kidney failure.10 The Spearman Rank’s correlation test showed that there
As many as 40% of diabetic patients can result in advanced was no significant correlation between HbA1c and systolic
stage of kidney disease.study aims to find correlations blood pressure. Also there was no significant correlation
between HbA1c levels with eGFR and blood pressure. between HbA1c and diastolic blood pressure. But, there
was a significant correlation between HbA1c and eGFR
Methods
with a weak positive correlation. The results can be seen
This analytic observational cross sectional study was in table 2.
conducted at Dr. Soetomo General Hospital, from June
2017 to October 2018. The population were all patients Table 2. Correlation between HbA1c with eGFR and blood
with T2DM in Dr. Soetomo General Hospital, Surabaya. pressure
there were 232 patients with 98 men and 134 women in HbA1c with r p
range January to May 2018. The sampling technique in this
eGFR 0,341 0,000*
research is conducted by purposive sampling.
The inclusion criteria in this study were patients with SBP -0,127 0,054
T2DM with or without its complications who had laboratory DBP -0,111 0,093
results including HbA1c levels and serum creatinine, and *: shows significant correlation with p<0,05
had blood pressure test results. The exclusion criteria were
patients with other type of diabetes mellitus. Type of data Discussion
collected is the secondary data that obtained from medical Our study shows that number of female patients was
records of patients with T2DM who hospitalized in Dr. 134 (57.8%) patients, more numbers in female patients
Soetomo General Hospital. The values of eGFR were compared to male patients. Two previous studies at at
obtained by using the MDRD (Modification of Diet in Arifin Achmad Hospital with higher proportion of female
Renal Disease) formula by entering serum creatinine, sex, than male.13 A higher percentage in women is caused
and age of the patient in the formula. by several factors, such as premenstrual syndrome, an
To test the correlation between HbA1c levels and increase in the Body Mass Index (BMI), and menopause.
eGFR, and the correlation between HbA1c levels and After menopause, there are changes in hormone levels,
systolic blood pressure and diastolic blood pressure, we especially estrogen and progesterone hormones that
used the Spearman’s Rank Correlation test and to test the influence blood sugar levels and increase abdominal fat
normality of data we used the Kolmogorov-smirnov test. and total body fat.14 Excess body fat is associated with an
Data will be analyzed by Statistical Product and Service increased risk of metabolic diseases.15
Solution (SPSS) for windows ver. 24 (IBM Corp.) with The results of this study corroborate the statement issued
p=0.05 and α=0.05 considered as significant. by Indonesian Endcrinology Association, that people ≥ 45
years should be tested for DM, because the risk of suffering
Results from glucose intolerance will begin to increase with age.12
There were more female (57,8%) than male with type 2 The study conducted by Fitri Nurmaya Sirait in 2018 with a
total of 167 people T2DM, showed that patients aged ≥ 45
 BIOMOLECULAR AND HEALTH SCIENCE JOURNAL 2019 OCTOBER, VOL 02 (02) 119

years tended to experience various complications compared increase in HbA1c and an increase in GFR are probably
to the age of <45 years. Various complications from patients caused by glomerular hyperfiltration in the early stages
≥ 45 years were acute complications of 66.7%, chronic of type 2 diabetes mellitus. In addition, it has also been
complications of 93.9%, mixed complications of 93.9% reported that after receiving therapy within a few months,
compared with patients <45 years. This may be caused a decrease in HbA1c levels is associated with a decrease
by an unhealthy lifestyle, including consumption of foods in GFR levels.22 Chronic kidney disease can be associated
high in fat and carbohydrates and lack of physical activity. with anemia. Anemia will be more severe if kidney
In this age group there has not been a decline in body function deteriorates, this is due to reduced erythroprotein
function as experienced in the age group ≥ 45 years, which production and poor food intake.23 So, HbA1c levels will
is a decrease in the function of the pancreas to produce decrease if anemia occurs due to reduced hemoglobin
insulin, thus increasing the risk of glucose intolerance.13 levels in the blood and short lifespan of erythrocyte cells.24
Some research says that there is no relationship between This result occurred because this study did not consider the
blood sugar levels and systolic hypertension.16 Different use of drugs used by the subjects.25
results stating that there was a relationship between HbA1c
levels and macrovascular complications, with the incidence Conclusion
of complications occurring most often being hypertension Type 2 diabetes mellitus patients age ≥ 45 years old are
as much as 35.4% of all samples of patients with T2DM.17 much more than < 45 years old with the ratio of 7 : 1. There
In the global DISCOVER study programme with 3 years are more female than male with type 2 diabetes mellitus.
prospective observational studies involving 15.992 T2DM This can occur due to menopausal factors in women
patients, microvascular and macrovascular complications which cause changes in hormone levels, increased BMI,
were reported in 18.9% (ARR: 14.5–23.5%) and 12.7% and increased total fat in the body. There was a significant
(ARR: 5.0–26.6%) of patients 18. correlation between HbA1c and eGFR.
About the correlation between HbA1c and diastolic
blood pressure, the same test results were conclude that there Conflict of Interest
was no association between hyperglycemia and diastolic The author stated there is no conflict of interest
hypertension.16 Another study has revealed that there is a
relationship between HbA1c and hypertension which leads References
to diastolic dysfunction due to right ventricular stiffness.
Patients with impaired glucose metabolism tend to have 1. Cheema, A. et al., 2014. Urbanization and prevalence of type
2 diabetes in Southern Asia: A systematic analysis. Journal of
an interfere with relaxation and increase stiffness of the Global Health, 4(1). Available at: http://www.jogh.org/documents/
heart muscle.19 AT2-receptor is increasingly shown to have issue201401/A4_Cheema_Final.pdf.
potential cardioprotective effects. ACE inhibition reduces 2. Trisnawati, S.K. & Setyorogo, S., 2013. Faktor Risiko Kejadian
left ventricular (LV) volumes, retards the progression of LV Diabetes Melitus Tipe II Di Puskesmas Kecamatan Cengkareng
Jakarta Barat Tahun 2012. Jurnal Ilmiah Kesehatan, 5(1), pp.6–11.
dilatation and hypertrophy and increases systolic function 3. Fatimah, R.N., 2015. “Diabetes Melitus Tipe 2”. J MAJORITY, vol.
in systolic dysfunction.20 Methylgloxal-derived Advanced 4, no. 5, 2015, pp.86–95.
Glycation End products (MG-AGEs) are produced post- 4. Yuliani, F., Oenzil, F. & Iryani, D., 2014. Hubungan Berbagai Faktor
myocardial infarction (MI) and identifies a causative role Risiko Terhadap Kejadian Penyakit Jantung Koroner Pada Penderita
Diabetes Melitus Tipe 2. Biomedika, 3(1), pp.37–40.
for their accumulation in the cellular changes, adverse 5. Kowalski, A., Krikorian, A. & Lerma, E. V., 2015. Diabetes and
remodelling and functional loss of the heart after MI.21 In chronic kidney disease. Disease-a-Month, 61(9), pp.378–386.
patients with diabetes mellitus, diastolic pressure is used to 6. Von Bibra, H. & St John Sutton, M., 2010. Diastolic dysfunction
determine the risk of nephropathy. in diabetes and the metabolic syndrome: Promising potential for
diagnosis and prognosis. Diabetologia, 53(6), pp.1033–1045.
High blood sugar levels can cause interactions between 7. Rosyada, A. & Trihandini, I., 2013. Determinan Komplikasi Kronik
hemodynamic and metabolic factors. In metabolic factors, Diabetes Melitus pada Lanjut Usia. Kesmas: Jurnal Kesehatan
abnormalities of glucose metabolism occur, such as Masyarakat Nasional, 7(9), pp.395–402. Available at: http://
the process of protein glycation, increase in the polyol jurnalkesmas.ui.ac.id/index.php/kesmas/article/view/11.
8. Seino, Y. et al., 2010. Report of the committee on the classification
pathway, and activation of the protein kinase C (PKC) and diagnostic criteria of diabetes mellitus. Journal of Diabetes
enzyme. Whereas in hemodynamic factors, the vasoactive Investigation, 1(5), pp.212–228.
hormone is angiotensin II which reacts. Both factors cause 9. From, A., Scott, C. & Chen, H., 2014. The Development of Heart
the cascade to activate intracellular cytokines such as the Failure in Patients with Diabetes Mellitus and Preclinical Diastolic
Dysfunction: A Population Based Study. , 55(4), pp.2–12.
Transforming Growth Factor-Beta (TGF-β) and end with 10. Pranandari, R., 2015. Faktor Risiko Gagal Ginjal Kronik Di Unit
increased vascular permeability. Activation of TGF-β will Hemodialisis RSUD Wates Kulon Progo. Majalah Farmaseutik,
stimulate protein expression, cause glomerular mesangium 11(2), pp.316–320.
expansion and generate Reactive Oxygen Species (ROS). 11. Di Lullo, L. et al., 2017. The treatment of type 2 diabetes mellitus in
patients with chronic kidney disease: What to expect from new oral
These things will trigger the activation of PKC and the hypoglycemic agents. Diabetes and Metabolic Syndrome: Clinical
Mitogen-Activated Protein Kinase (MAPK) pathway. Research and Reviews, 11(2016), pp.S295–S305. Available at: http://
These two things will cause activation of prosclerotic dx.doi.org/10.1016/j.dsx.2017.03.005.
cytokines, the Connective Tissue Growth Factor (CTGF), 12. PERKENI, 2015. Konsensus Pengendalian dan Pencegahan Diabetes
Melitus Tipe 2 di Indonesia 2015, Available at: http://pbperkeni.or.id/
which stimulates the formation of fibronectin and collagen, doc/konsensus.pdf.
leading to an increase in intrarenal pressure, increase in 13. Sirait, F., 2018. Karakteristik Penderita Diabetes Mellitus Tipe
vascular permeability, proteinuria, decrease in EGFR.19 2 Dengan Komplikasi Yang Rawat Inap Di Rumah Sakit Santa
Other research showed a significant relationship between Elisabeth Medan Tahun 2016. Universitas Sumatera Utara, Medan,
Sumatera Utara.
HbA1c and GFR with the strength of a positive correlation,an
 BIOMOLECULAR AND HEALTH SCIENCE JOURNAL 2019 OCTOBER, VOL 02 (02) 120

14. Karyati, S. & Astuti, P., 2016. Usia Menopause dan Kejadian Diabetes (2017) 112: 57. https://doi.org/10.1007/s00395-017-0646-x
Melitus. , 7(2), pp.27–31. 22. Sukohar, A., Damara, A. & Graharti, R., 2018. Hubungan Nilai
15. Davis, S.R. et al., 2012. Memahami Peningkatan Berat Badan saat HbA1c dengan Laju Filtrasi Glomerulus ( EGFR ) pada Pasien
Menopause. CLIMACTERIC, 14, pp.1–31. Diabetes Melitus Tipe 2 di Rumah Sakit Umum Daerah H . Abdul
16. PERKENI, 2015. Konsensus Pengendalian dan Pencegahan Diabetes Moeloek Bandar Lampung Correlation Between HbA1c Value And
Melitus Tipe 2 di Indonesia 2015, Available at: http://pbperkeni.or.id/ Glomerular Filtration Rate ( GFR ) in Type 2 Diabetes Mellitus. , 2,
doc/konsensus.pdf. pp.37–41.
17. Fitrah, A., 2017. Hubungan kadar gula darah dengan tekanan darah 23. Rigalleau, V. et al., 2006. Glucose control influences glomerular
pada pasien diabetes melitus tipe-2 di rumah sakit umum pusat haji filtration rate and its prediction in diabetic subjects. Diabetes Care,
adam malik tahun 2016. 29(7), pp.1491–1495.
18. Gomes, M.B. et al., 2019. Treatment of type 2 diabetes mellitus 24. Nura, M., Bintanah, S. & Handarsari, E., 2014. Hubungan Asupan
worldwide : Baseline patient characteristics in the global DISCOVER Protein Dengan Kadar Ureum , Kreatinin , dan Kadar Hemoglobin
study. Diabetes Research and Clinical Practice, 151, pp.20–32. Darah pada Penderita Gagal Ginjal Kronik Hemodialisa Rawat Jalan
Available at: https://doi.org/10.1016/j.diabres.2019.03.024. Di RS Tugurejo Semarang. , 3(April), pp.22–32.
19. Richter, M.J. et al., 2016. The clinical significance of HbA1c in 25. Busch, M. et al., 2016. Glycaemic control and antidiabetic therapy in
operable chronic thromboembolic pulmonary hypertension. PLoS patients with diabetes mellitus and chronic kidney disease – cross-
ONE, 11(3), pp.1–15. sectional data from the German Chronic Kidney Disease (GCKD)
20. Anavekar, N. S., & Solomon, S. D. (2005). Angiotensin II receptor cohort. BMC Nephrology. Available at: http://dx.doi.org/10.1186/
blockade and ventricular remodelling. Journal of the Renin- s12882-016-0273-z.
Angiotensin-Aldosterone System, 43–48. https://doi.org/10.3317/ 26. Davis, S.R. et al., 2012. Memahami Peningkatan Berat Badan saat
jraas.2005.006 Menopause. CLIMACTERIC, 14, pp.1–31.
21. Blackburn, N.J.R., Vulesevic, B., McNeill, B. et al. Basic Res Cardiol