Diabetes Mellitus as the Main Factor of Restenosis: Literature Review

Introduction: Patients who have had cardiac stents have the risk of experiencing restenosis. The percentage of patients experiencing restenosis in RSUD Dr. Soetomo Surabaya in 2017 reached 43.75%. Not yet known the main factors causing restenosis affect the increase in mortality due to restenosis. Several studies suggest that diabetes mellitus is the factor that most consistently increases the risk of restenosis. This requires further research with the literature review method to analyze the continuity of the journals found.


INTRODUCTION
Patients who have had a heart stent inserted are at risk of experiencing restenosis. Restenosis is defined as narrowing of the vessel lumen to> 50% occlusion.
Restenosis occurs on average 3-6 months after PCI.
Several studies suggest that diabetes mellitus is the factor that most consistently increases the risk of restenosis (Buccheri et al., 2016). The percentage of patients experiencing restenosis reached 33 (Patrick W. Serruys, MD;John D. Rutherford, 2016). Whereas in Indonesia, especially at the Dr. Soetomo Surabaya Hospital in 2017, the results obtained from 32 patients after the installation of stents who were treated in April, 43.75% of patients experienced restenosis (Agustin, 2017).
Diabetes mellitus has a major role in determining and growing the restenosis process. This is due to the prothrombotic environment of the coronary vessels, including increased blood viscosity and decreased biological activity of antithrombin II, fibrinogen and factor VII as well as increased platelet aggregation which can play a role in restenosis.
Additionally, the effects of stimulatory growth factors such as insulin-like growth factors on VSMCs can lead to a greater degree of neointimal hiperplasia (Buccheri et al., 2016). Research on the factors that cause restenosis is widely found, where diabetes mellitus is one of the factors. However, there are no specific studies regarding diabetes mellitus as a major factor in restenosis. Writing this literature review aims to analyze the continuity of these journals so that it can be considered that diabetes mellitus is the main factor for restenosis.

RESULT
The total number of journals that are suitable and subsequently reviewed in this study is 15 journals.
The distribution of sources used is 8 Scopus journals, 2 CINAHL journals and 5 ProQuest journals. All journals were published in the last five years (2015-2020) and most published in 2017 in China.
Fifteen journals were reviewed according to the results found, six journals said that diabetes mellitus was a factor in restenosis.
Two journals reviewed stated that body mass index is the risk of restenosis. Body mass index is also known to be a risk factor for diabetes mellitus (Kammler et al., 2017). Two journals that strongly argue that DM is not a predictor of restenosis. DM is not considered a predictor of restenosis in the short or long term.

DISCUSSION
Diabetes mellitus (DM) is a condition in which metabolic disorders occur, which can be in the form of damage to the pancreas, resulting in insulin deficiency or insulin resistance in the body's cells so that the impact of both conditions is an increase in blood glucose. Patients with ScR had diabetes more frequently (44% vs 20%; p <0.001) (Polimeni et al., 2017). Clinical factors such as age and diabetes mellitus status have been confirmed to increase the risk of restenosis (Kang et al., 2015).
Diabetes mellitus is a prognostic risk factor after stenting because diabetes mellitus is predicted to be a higher risk for restenosis. Patients with diabetes mellitus have an increased production of Advanced Glycation End (AGE) which can increase reactive oxygen and accelerate arterial veins and atherosclerosis, and ultimately lead to restenosis.
Thus diabetes mellitus is predicted to be higher in increasing the risk of restenosis (J. Zhao et al., 2020).   (Rai et al., 2015). Regarding the FFR, it was suggested that the post-stent FFR could be used to predict restenosis. However, it was also stated that the FFR is not the right tool for DM patients. This is because the FFR is not significant because there are several confounders that affect the coronary artery flow rate such as diabetes mellitus or hypertension. On the other hand, the prevalence of hypertension and DM was found to be higher in patients with coronary stenosis, which serves as a confounding factor because it is associated with higher microvascular resistance and potentially a higher FFR value.
Previous research also states that diabetes mellitus has a major role in determining and growing the restenosis process. Prothrombotic from diabetic coronary vessels, including increased blood viscosity, decreased biological activity of antithrombin II, fibrinogen and factor VIII and increased platelet aggregation, can play a role in the occurrence of DM.
In addition, the effects of a stimulatory growth factor such as insulin-like growth factor-1 on VSMCs can lead to a greater degree of neointimal hyperplasia. Research (Yin et al., 2017)

CONCLUSION
The results of a review of 15 journals found that diabetes mellitus was a factor that appeared consistently and had a role in the incidence of In-stent restenosis after interventional treatment of carotid artery stenoses: a long-term follow-up of a single center cohort. Clinical Research in Cardiology, 106