IJCS | Volume 33, Nº1, January / February 2019

15 Lott Bezerra et al. Insulin use and infective endocarditis Int J Cardiovasc Sci. 2020;33(1):14-21 Original Article The association between DM and IE is still controversial in the literature. DM has been indicated as an independent predictor of in-hospital mortality in the studies by Chu et al. 3 and Chrillo et al., 7 and according to Movahed et al., 8 IE was more prevalent in patients with Type II DM, when compared to non- diabetic patients. On the other hand, although Moreno et al. 9 and Wallace et al. 10 found higher mortality values in diabetic patients with IE in relation to non-diabetic ones, there was no statistical significance to corroborate this association. Other authors have shown that DMwas associated with a higher risk of septic shock in IE, but an association with higher mortality was not observed. 11 However, regarding the use of insulin by diabetic patients and a possible association with IE, there was little evidence in the literature that considered this variable; only two observational studies did it, one carried out by Duval et al. 12 and another by Olmos et al. 11 The first one showed that insulin users showed significant differences regarding in-hospital mortality and the proportion of IE by Staphylococcus sp when compared to DM patients receiving an exclusive oral hypoglycemic drug and non-diabetic patients. The results of the second study were discordant, since there were no differences in prognosis and microbiology. It should be noted that the study by Olmos et al. 11 included only cases of IE in the left heart chamber. For the diagnosis of IE, the Duke Criteria were proposed by Durack et al. 13 in 1994, which represented an advance in the understanding of IE and which included “intravenous drug use” as a minor criterion. However, Li et al., 14 in 2000, proposed changes that gave rise to the modified Duke Criteria, with the minor criterion “intravenous drug use” being replaced by “injectable drug use”. Therefore, by definition, 15 any subcutaneous, intramuscular or intravenous injectable substance would also be considered a minor and predisposing criterion for IE, such as insulin. We emphasize that the reason for the change was not addressed by Li et al. 14 Moreover, considering the pathophysiological aspects of IE, in which bacteremia has an essential role, it is possible that the use of subcutaneous insulin has characteristics that are close to those of the group of patients who use intravenous drugs. The correlation between intravenous drug use and IE is explained by the introduction of microorganisms and particles into the circulation during the injection, which damage and colonize the heart valves. 16 In the case of insulin use, despite the subcutaneous route of administration, it would be plausible the hypothesis of bacteremia occurring in certain situations, such as hematoma at the injection site, a frequently described complication 17-19 with the use of inadequate techniques and one that represents vascular damage associated with a solution of continuity with the skin microbiota. In fact, Tuazon et al. 20 have shown that insulin use increases the risk of mucocutaneous colonization by S. aureus . Skin infections such as abscesses have also been described in injection sites in insulin users, and according to Binswanger et al., 21 the subcutaneous space can be colonized by multiple microorganisms that are introduced by non-sterile drug injections. The study by Lipsky et al. 22 demonstrated bacteremia in 15 to 19% of patients with this type of infection and the most often involved microorganism was S. aureus . Patients who are insulin-users also have the concomitant need for frequent self-monitoring of blood glucose levels through finger blood collection, which could facilitate bacteremia, as the capillary bed is exposed to the external environment. Cases of sepsis and osteoarthritis due to abscess focus in the fingers of patients who were inadequately self-monitoring blood glucose have already been reported. 23,24,25 Thus, the aim of the study is to evaluate and compare the microbiological, valvular and outcome aspects of IE in diabetic patients who are insulin users or non-insulin users or are not diabetic, in addition to comparing the results with the current literature. Method Study population The population consisted of 211 patients with probable or definitive IE admitted at in three tertiary care centers in themunicipalities of BeloHorizonte and Ipatinga, state of Minas Gerais, Brazil, between 2003 and 2015. The inclusion criteria were: patients admitted between 2003 and 2015 in three hospitals, who were diagnosed with definitive or probable IE, according to the modified Duke criteria. 13 Patients whomet the criteria for Definitive or Probable IE were included in the database. The exclusion criteria were: patients who were transferred to another tertiary care center or who were still hospitalized during the data collection period. Medical records with insufficient data were also excluded.