Diabetes and erectile dysfunction: The relationships with health literacy, treatment adherence, unrealistic optimism, and glycaemic control

The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM.


| MATERIALS AND METHODS
This prospective observational study enroled 167 consecutive patients from November 2021 to March 2022. All patients were admitted to the clinic of Endocrinology and Diabetes of the University Campus Bio-Medico of Rome because they were affected by T2D or prediabetes. The inclusion criteria were (1) male sex, (2) age be- The choice of the T2D or preDM pharmacological treatment was based on patient characteristics (age, glycaemic compensation, comorbidities) according to AMD-SID 11 and American Diabetes Association 12 guidelines.
Patients receiving metformin plus one of the other treatments were clustered according to the second one. Patients receiving insulin plus one or more than one of the other treatments were clustered in the insulin group, as previously described. 13 Furthermore, blood samples were collected at 8:00 AM and plasma levels of total testosterone and glycosylated haemoglobin (HbA1c) were determined. Chemiluminescence microparticle immunoassay and immunoassay (CLIA) were used.
To assess erectile dysfunction, all patients completed the International Index of Erectile Function-5 questionnaire, a validated tool to outline ED (score: no ED > 21, mild ED 17-21, mild to moderate ED 12-16, moderate ED 8-11, severe ED 5-7). 14 The IIEF-5 questionnaire was self-completed by each participant in a dedicated hospital room without possible influence and/or interference from physicians or other health professionals and was completed using pen and paper. Patients who reported no regular sexual intercourse in the past 6 months, as required by the IIEF-5 questionnaire, 15 were excluded.
Health literacy was assessed using the following questions: Question 1: "Are you aware that ED is a complication T2D?" (yes/ not). Question 2: "If you knew that ED is a complication of T2D, would you follow your T2D treatment (diet and/or pharmacological) better"? (yes/not). In addition, the following validated question was used to assess unrealistic optimism 16 : Question 3: "Do you believe that your risk of developing ED due to diabetes is higher than that of other patients with diabetes of your same age?" (No, I believe my risk is lower/I believe my risk is the same/yes, I believe my personal risk is higher). Finally, the following validated question was used to assess treatment adherence 17 : Question 4: "How much have you followed the prescribed treatments in the last month?" (Never/Less than half the time/About half the time/More than half the time/Always).
The study was conducted in respect of the ethical standards of the Declaration of Helsinki (2000) and was approved by the Ethics Committee of the LAZIO 2 Azienda Sanitaria Locale Roma 2 (Protocol n. 0247297, Study 171/21).

| STATISTICAL ANALYSIS
Continuous data were described as mean � standard deviation (SD) with minimum and maximum values. The normal distribution of data was assessed with the Shapiro-Wilk test, and t-or ANOVA tests were used to detect statistically significant differences between continuous data. Categorical data were described as absolute numbers and percentages. Fisher's exact or chi-squared tests were used to assess statistically significant differences. p-values<0.05 defined statistically significant differences. The software SPSS (IBM, USA) was used for statistics.

| RESULTS
A total of 167 patients with T2D or pre-DM were evaluated. Of these, 4 patients reported not having sex, and 7 did not complete the interview. Thus, the final sample consisted of 156 patients. The baseline characteristics of patients are described in Table 1 -3 of 7 others (p < 0.01). Finally, to Question 4, 4.5% (n = 7) of patients answered "Never", 21.8% (n = 34) "Less than half the time", 46.8% (n = 73) "About half the time", 19.9% (n = 31) "More than half the time," and 7.1% (n = 11) "Always." The prevalence of the response "About half the time" was significantly higher than the others (p < 0.01) (Figure 1).

After evaluating the presumed associations between responses
to Questions 1-4 and IIEF5 scores (each as a value from 5 to 25 and categorised as no ED, mild ED, mild to moderate ED, moderate ED, and severe ED), the only significant difference was a higher IIEF-5 score in patients who responded "No" to Question 1 (17.5 � 4.2, range 6-25, vs. 14.7 � 5.3, range 5-25; p < 0.01; Figure 2). No other significant associations were observed among the remaining parameters (total testosterone levels and TRT included).

| DISCUSSION
In this study, we examined the associations between health literacy, unrealistic optimism, and adherence to glycometabolic disease management in relation to ED in a group of male patients with T2D or preDM.
Erectile dysfunction occurrence was very high in the T2D population, ranging from 35% to 90%. 2,3 Both T2D and preDM may be responsible for sexual dysfunction with different pathogenetic mechanisms. 4,5,18 Furthermore, T2D treatment seems to be closely associated with ED. 13,19 Health literacy plays an important role in the knowledge about T2D, both in self-care and glycaemic control. 20 In this study, most patients answered "yes" to both Question 1 and Question 2, indicating high health literacy: this response seems to highlight that the majority of patients were adequately informed about their disease.
Patients with inadequate health literacy were described as having a higher incidence of chronic conditions because they could not correctly recognise the symptoms of T2D and T2D complications. 21 Interestingly, patients who answered "No" to Questions 1, indicating low knowledge of ED as a complication of T2D, had a higher IIEF-5 score than individuals who answered "Yes". This result, which cannot be substantiated because of the lack of available data in the literature, raises speculation about an explanation. This result might suggest that good healthy literacy does not adequately protect against the onset of ED anyway. On the other hand, as with other diseases, higher health literacy could have a positive effect on ED diagnosis. In this regard, Demirbas et al 22 found that as health literacy increases, ED becomes more important to patients. In line with this finding, sociocultural levels have also been described as a determinant of increased incidence and prevalence of ED. 23 Finally, good health literacy is known to lead to better self-control in preventing or updating T2D complications.
Interestingly, we found that patients with lower health literacy had significantly higher BMI. Previous studies have shown that lower health literacy is associated with lower frequency of healthpromoting behaviours, higher frequency of risky health behaviours, and higher BMI. 24 Curiously, we found a trend of low healthy literacy in patients who had already taken PDE5i; we speculate that this could depend on the fact that by assuming a "symptomatic" therapy, patients did not investigate the organic causes of ED. In this regard, the wide and early use of PDE5i , improving the erectile function, has led to a significant number of missed diagnoses of this underlying symptom. 25 The evaluation of unrealistic optimism, defined as the erroneous judgement of personal risk as lower than the risk of others, 16 was lower in the majority of the population; therefore, most patients believed that their personal risk was higher than that of others.
However, approximatively 25% of patients showed low adherence to T2D treatment; indeed, they responded that they never followed the physician's instructions or followed them less than half of the time.
On the other hand, higher adherence to treatment was found in patients who reported regular physical activity and followed a diet, and in patients with a family history of T2D. The first finding was expected as patients with correct lifestyle habits are generally more willing to follow physician instructions. Indeed, self-care (i.e., physical activity and medication adherence) is essential for the prevention of complications in patients with T2D. 26 As for the second aspect, family experience is usually considered as a source of knowledge. On the contrary, a recent study investigating factors associated with glycaemic control in patients with type 1 diabetes mellitus found that a family history of T2D worsened metabolic compensation. 27 Similar results were found in patients with T2D; specifically, family history of T2D was significantly positively associated with awareness but negatively associated with control. 28 When considering anti-diabetic treatment, we found that patients treated with insulin had higher health literacy than patients not treated with other medications. This is probably due to the fact that patients treated with insulin have a longer history of the disease, which increases their knowledge. Indeed, patients treated with insulin must exert more effort than patients orally treated with antihyperglycaemic drugs to achieve optimal glycaemic control because they must adjust the dosage and frequency of insulin injections, selfmonitor blood glucose, and avoid hypoglycaemia. 29 Anyway, we previously observed that across all treatment groups, the only significant difference in the IIEF-5 score was a higher mean value in patients using GLP-1ra compared to patients on insulin treatment. 13 The effect of insulin on sexual function that emerged from the study was difficult to compare to other studies, which were mainly based DEFEUDIS ET AL.