Correlation of Hypoxia-Inducible Factor-1α Level with Control Glycemic in Type 2 Mellitus Patients with Malignancy and Without Malignancy


  • Rusdiana Rusdiana Department of Biochemistry, Medical Faculty, Universitas Sumatera Utara, Jl. Dr. Mansur No. 5, Medan, Indonesia
  • Maya Savira Department of Physiology, Medical Faculty, Universitas Sumatera Utara, Jl. Dr. Mansur No.5, Medan, Indonesia
  • Kamal Basri Siregar Department of Surgery, Oncology Subdivision, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Sry Suryani Widjaja Department of Biochemistry, Medical Faculty, Universitas Sumatera Utara, Jl. Dr. Mansur No. 5, Medan, Indonesia
  • Dedi Ardinata Department of Physiology, Medical Faculty, Universitas Sumatera Utara, Jl. Dr. Mansur No.5, Medan, Indonesia



Diabetes mellitus Type 2, Malignancy, Fasting blood sugar, HbA1c, Hypoxia-inducible factor 1-alpha


BACKGROUND: Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Malignancy is one of the most common causes of death in the world. T2DM is one of the risk factors for malignancy. This is caused by an increase in blood glucose levels (hyperglycemia) which will cause tissue hypoxia which can lead to malignancy. The cell adaptation response to hypoxia is relaxed by a marker called hypoxia-inducible factor-1 alpha (HIF-1α), where a condition converts hyperglycemia to a loss of cellular response to hypoxia in most complications of diabetes.

AIM: The aim of this study was to determine level HIF-1α at T2DM with malignancy, where this study used the samples of the T2DM patients with malignancy and T2DM without malignancy.

METHODS: The cross-sectional study design used the 89 samples of DM patients with and without malignancy who attended Murni Teguh Hospital in Medan of Indonesia country. The inclusion criteria of the samples were all the patients diagnosed with T2DM with or without malignancy, both the sexes. Body mass index, blood pressure, disease history, and socioeconomic status were recorded. The laboratory parameters, including fasting blood sugar (FBS) and HbA1c, were examined by Murni Teguh Hospital Laboratory and HIF-1α; we examined by ELISA methods in the laboratory Medical Faculty, Sumatera Utara Universitas.

RESULTS: In this study, we found that there was no significant correlation between HIF-1α with FBS and HbA1c (p > 0.005), but we found that there was a significant correlation HbA1c with FBS (p < 0.005).

CONCLUSION: The results of the study revealed HIF-1α at the both of the group of the samples even in the relative small amounts until a large amounts in the serum, but we found that there was no correlation significantly between HIF-1α and glycemic index (HbA1c and FBS), while there was correlation significantly between Hba1c and FBS.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Kulie T, Slattengren A, Redmer J, Counts H, Eglash A, Schrager S. Obesity and women’s health: an evidence-based review. J Am Board Fam Med. 2011;24(1):75-85. https://doi. org/10.3122/jabfm.2011.01.100076 PMid:21209347

American Diabetes Association. Diagnosis and Classification of diabetes Mellitus. New York: American Diabetes Association; 2009.

Republik Indonesia. Badan Penelitian dan Pengembangan Kesehatan Kementrian Kesehatan. Jakarta, Indonesia: Republik Indonesia; 2013.

International Diabetes Federation. Riset Kesehatan Dasar Jakarta. F Diabetes Atlas. International Diabetes Federation; 2013. Available from: [Last accessed on 2019 Mar 10].

Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev. 2003;23(2):117-45. https://doi. org/10.1002/med.10024 PMid:12500286

Onitilo AA, Engel JM, Glurich I, Stankowski RV, Williams GM, Doi SA. Diabetes and cancer I: Risk, survival, and implications for screening. Cancer Causes Control. 2012;23(6):967-81. PMid:22552844

García-Jiménez C, García-Martínez JM, Chocarro-Calvo A, De la Vieja A. A new link between diabetes and cancer: Enhanced WNT/β-catenin signaling by high glucose. J Mol Endocrinol. 2014;52(1):R51-66. jme-13-0152 PMid:24049067

Stocks T, Rapp K, Bjørge T, Manjer J, Ulmer H, Selmer R, et al. Blood glucose and risk of incident and fatal cancer in the metabolic syndrome and cancer project (Me-Can): Analysis of six prospective cohorts. PLoS Med. 2009;6(12):e1000201. PMid:20027213

Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schünemann HJ, et al. Fasting glucose is a risk factor for breast cancer: A prospective study. Cancer Epidemiol Biomarkers Prev. 2002;11:1361-8. PMid:12433712

Saydah SH, Platz EA, Rifai N, Pollak MN, Brancati FL, Helzlsouer KJ. Association of markers of insulin and glucose control with subsequent colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2003;12(5):412-8. PMid:12750235

Jiang Y, Ben Q, Shen H, Lu W, Zhang Y, Zhu J. Diabetes mellitus and incidence and mortality of colorectal cancer: A systematic review and meta-analysis of cohort studies. Eur J Epidemiol. 2011;26(11):863-76. s10654-011-9617-y PMid:21938478

Noto H, Tsujimoto T, Sasazuki T, Noda M. Significantly increased risk of cancer in patients with diabetes mellitus: A systematic review and meta-analysis. Endocr Pract. 2011;17(4):616-28. PMid:21454235

Min H, Kornelia P. Microenvironmental regulation of cancer development. Curr Opin Genet Dev. 2008;18(1):27-34. https://

Pernicova I, Korbonits M. Metformin: Mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014;10(3):143-56. PMid:24393785

Bodmer M, Meier C, Krahenbuhl S, Jick SS, Meier CR. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 2010;33:1304-8. dc09-1791 PMid:20299480

Krentz AJ, Bailey CJ. Oral antidiabetic agents: Current role in Type 2 diabetes mellitus. Drugs. 2005;65:385-411. https://doi. org/10.2165/00003495-200565030-00005 PMid:15669880

Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with Type 2 diabetes: Systematic review. PLoS One. 2013;8:e71583. PMid:23936520

Zordoky BN, Bark D, Soltys CL, Sung MM, Dyck JR. The anti-proliferative effect of metformin in triple-negative MDA-MB-231 breast cancer cells is highly dependent on glucose concentration: implications for cancer therapy and prevention. Biochim Biophys Acta. 2014;1840(6):1943-57. bbagen.2014.01.023 PMid:24462945

Ece H, Cigdem E, Yuksel K, Ahmet D, Hakan E, Oktay TM. Use of oral antidiabetic drugs (Metformin and Pioglitazone) in diabetic patients with breast cancer: How does it effect on serum Hif-1 alpha and 8Ohdg levels? Asian Pac J Cancer Prev. 2012;13(10):5143-8. apjcp.2012.13.10.5143 PMid:23244125

Giovannucci E. Insulin, insulin-like growth factors and colon cancer: A review of the evidence. J Nutr. 2001;131(11 Suppl):3109S-20S. jn/131.11.3109s PMid:11694656

Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009;69(19):7507-11. 5472.can-09-2994 PMid:19752085

Mcpherson K, Steel CM, Dixon JM. 5 Breast cancer epidemiology, risk factors, and genetics. ABC of Breast Dis. 2009;572:24.

Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: A consensus report. CA Cancer J Clin. 2010;60(4):207-21. PMid:20554718

Katherine LT, Turley H, Gatter KC, Maxwell PH, Pugh CW, Ratcliffe PJ, et al. The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol. 2000;157(2):411-21. s0002-9440(10)64554-3 PMid:10934146

Harding JL, Shaw JE, Peeters A, Cartensen B, Magliano DJ. Cancer risk among people with Type 1 and Type 2 diabetes: Disentangling true associations, detection bias, and reverse causation. Diabetes Care. 2015;38(2):264-70. https://doi. org/10.2337/dc14-1996 PMid:25488912

Li QF, Xu H, Sun Y, Hu R, Jiang H Induction of inducible nitric oxide synthase by isoflurane post-conditioning via hypoxia inducible factor1aduring tolerance against ischemic neuronal injury. Brain Res. 2012;1451:1-9. brainres.2012.02.055 PMid:22445062

Thangarajah H, Yao D, Chang EI, Shi Y, Jazayeri L, Vial IN, et al. The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proc Natl Acad Sci USA. 2009;106(32):13505-1. pnas.0906670106 PMid:19666581

Hoo Y, Mahmoud AA. Hypoxia inducible factor-1α in Type 2 diabetes mellitus with microalbuminuria and retinopathy. Majalah Kedokt Bandung Bandung Med J. 2014;46(2):100-5.

Lin M, Chen Y, Jin J, Hu Y, Zhou KK, Le YZ, et al. Ischaemia-induced retinal neovascularisation and diabetic retinopathy in mice with conditional knockout of hypoxia-inducible factor-1 in retinal Muller cells. Diabetologia. 2011;54(6):1554-66. https:// PMid:21360191

Liang J, Qian Y, Xu D, Yin Q, Pan HJ. Serum tumor markers: Hypoxiainducible factor-1α HIF-1α and vascular endothelial growth factor, in patients with non-small cell lung cancer before and after intervention. Asian Pac J Cancer Prev. 2013;14(6):3851-4. PMid:23886195

Zhang Z, Yan J, Shi H. Role of hypoxia inducible factor 1 in hyperglycemia exacerbated blood-brain barrier disruption in ischemic stroke. HHS Public Access. 2016;95:82-9. https://doi. org/10.1016/j.nbd.2016.07.012 PMid:27425889

Bento CF, Pereira P. Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes. Diabetologia. 2011;54:1946-56. s00125-011-2191-8 PMid:21614571

Catrina SB, Okamoto K, Pereira T, Brismar K, Poellinger L. Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes. 2004;53(12):3226-32. PMid:15561954

Scheid A, Wenger RH, Schaffer L, Camenisch I, Distler O, Ferenc A, et al. Physiologically low oxygen concentrations in fetal skin regulate hypoxia-inducible factor 1 and transforming growth factor-3. FASEB J. 2002;16(3):411-3. https://doi. org/10.1096/fj.01-0496fje PMid:11790723

Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes PMid:19620249

Chaturvedi P, Gilkes DM, Wong CC, Luo W, Zhang H, Wei H, et al. Hypoxia- inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. J Clin Invest. 2013;123(1):189-205. https://doi. org/10.1158/1538-7445.am2013-505 PMid:23318994

Yeung SJ, Pan J, Lee MH. Roles of p53, Myc and HIF-1 in regulating glycolysis: The seventh hallmark of cancer. Cell Mol Life Sci. 2008;65(24):3981-999. s00018-008-8224-x PMid:18766298

Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8(6):519-30. jgp.8.6.519 PMid:19872213

Zhang H. HIF-1 suppresses lipid catabolism to promote cancer progression. Mol Cell Oncol. 2015;2(4):980184. 10.4161/23723556.2014.980184 PMid:27308514

Sakkinen PA, Wahl P, Cushman M, Lewis MR, Tracy RP. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors ininsulin resistance syndrome. Am J Epidemiol. 2000;152(10):897-907. aje/152.10.897 PMid:11092431

Jiang F, Tang YT, Guo L, Jiao XY. The role of insulin-like growth factor i and hypoxia inducible factor 1α in vascular endothelial growth factor expression in Type 2 diabetes. Ann Clin Lab Sci. 2013;43(1):37-44. hypertensionaha.115.06412 PMid:23462604

Xing F, Okuda H, Watabe M, Kobayashi A, Pai SK, Liu W, et al. Hypoxia induced Jagged2 promotes breast cancer metastasis and self-renewal of cancer stem-like cells. Oncogene. 2011;30(39):4075-86. PMid:21499308




How to Cite

Rusdiana R, Savira M, Siregar KB, Widjaja SS, Ardinata D. Correlation of Hypoxia-Inducible Factor-1α Level with Control Glycemic in Type 2 Mellitus Patients with Malignancy and Without Malignancy. Open Access Maced J Med Sci [Internet]. 2020 Apr. 10 [cited 2024 Feb. 25];8(B):408-13. Available from:

Most read articles by the same author(s)

1 2 3 > >>