Longitudinal Assessment of Quality of Life in Patients With Type 2 Diabetes and Self-Reported Erectile Dysfunction

The study design has already been described in detail elsewhere (1). Briefly, physicians were identified in all regions of Italy and selected according to their willingness to participate in the project. Overall, 114 diabetes outpatient clinics and 112 general practitioners participated in the study.

All patients with type 2 diabetes were considered eligible for this project, irrespective of age, duration of diabetes, and treatment. In diabetes outpatient clinics, patients were sampled by using random lists, stratified by patient age (<65 or ≥65 years). Each center was asked to recruit at least 30 patients, whereas general practitioners enrolled only those patients for whom they were primarily responsible for diabetes care. Clinical information was abstracted from clinical records by the participating physicians and reported in ad hoc forms. Data were collected at baseline and at 6-month intervals for 3 years.

Baseline clinical variables referred to the last value in the previous 12 months. Because normal ranges for HbA_1c varied among the different centers, the percentage change with respect to the upper normal value (actual value/upper normal limit) was estimated and multiplied by 6.0. Cardiovascular disease (CVD) included myocardial infarction, angina, coronary revascularization procedures, stroke, and lower limb complications (claudication, ulcer, gangrene, amputation, and aortic-femoral revascularization procedures).

All subjects were asked to complete a questionnaire upon entry into the study and at 6-month intervals over a period of 3 years. The questionnaire was self-administered and then sent anonymously to the coordinating center in prepaid envelopes. The matching between clinical data and the questionnaire was made possible through a code put by the physician on both sources of information. No other details on patient identity were contained neither in the questionnaire nor in clinical data.

The presence of ED was investigated by asking the patient how often he had experienced problems in achieving and maintaining an erection during the past 6 months, with responses calibrated on a 5-level scale (from never to more than once per week). We considered only those patients who reported frequent erectile problems (almost every week or more than once a week) as being affected by ED. Incident cases of ED were considered those patients without ED at baseline who reported frequent erectile problems during the follow-up. The presence and severity of diabetes complications and comorbidities were summarized by using the Total Illness Burden Index (TIBI), a widely used comorbidity measure specifically developed for outpatient populations (6).

QoL was assessed using the SF-36 Health Survey, a generic measure covering eight dimensions: physical functioning, role limitations caused by physical health problems, bodily pain, general health perception, vitality, social functioning, role limitations caused by emotional health problems, and mental health (7). Scores on all the subscales are transformed linearly to a possible range of 0–100; higher scores indicated more favorable physical functioning/psychological well-being. These eight domains may be further aggregated into two summary measures: the physical component summary measure and the mental component summary measure (8).

The Center for Epidemiologic Studies–Depression (CES-D) Scale is a self-reported measure of depression composed of 20 items addressing symptoms of depression during the previous 4 weeks. Values of the CES-D Scale range from 0 to 60 with higher values indicating more severe depressive symptoms (9).

We evaluated the quality of sexual life using the Sexual Life Questionnaire composed of six items. The score ranges between 0 and 100, with higher values indicating better quality of sexual life. Details on the questionnaire validation have been reported in a previous paper (1).

Patients’ characteristics according to the presence/development of ED were compared using the χ² test for categorical variables and the Mann-Whitney U test for continuous variables. Changes in QoL scores during the study were calculated as the difference between baseline and last follow-up value and compared using the paired t test. Effect sizes were calculated by dividing the changes in each QoL score by the SD of that score estimated at baseline on the entire sample.

To account for the hierarchical nature of the data (repeated measurements within patients) and to control simultaneously for the possible confounding effects of the different variables, we utilized multivariate multilevel linear models (10,11). In our longitudinal analysis, which evaluated factors associated with a decline in QoL measures, multilevel methods allowed to appropriately model within- and between-patient variability (12).

Among baseline patient characteristics, the following sociodemographic and clinical characteristics were considered: age, school education, marital status, diabetes duration, previous history of a cardiovascular event, diabetes therapy, hypertension, presence, and severity of comorbidity (TIBI). We considered the occurrence of ED and the incidence of CVD events during the follow-up as time-dependent covariates.

Results are expressed in terms of standardized β parameters with the relative P value. Standardized β parameters indicate the changes over time in QoL measures with respect to baseline for patients without ED and those with ED at baseline. For patients who developed ED during the follow-up, the β parameters show the average change from before to after the development of ED. All the analyses were performed using SAS Statistical Package, version 8.2 (13).

The study involved 1,456 patients, of whom 500 patients (34%) reported frequent erectile problems at study entry and 192 patients (13.2%) developed ED during the follow-up. Patients’ characteristics according to the presence or development of ED are reported in Table 1. Patients who developed ED were older; had longer duration of diabetes, worse metabolic control, and a higher TIBI score; and were more often treated with insulin and affected by hypertension, neuropathy, micro- or macroalbuminuria, or CVD compared with those without ED. With respect to patients with ED at baseline, those who developed ED during the follow up were less often treated with insulin, less likely to have retinopathy, and showed a lower TIBI score.

The analysis of QoL scores during 3 years of follow-up showed that no major changes were present among patients without ED, except for a slight improvement in depressive symptoms (P = 0.016) (Table 2). In individuals with ED at baseline we documented a worsening in the physical dimensions of the SF-36, which reached the statistical significance for physical functioning (P = 0.003) and the physical component summary measure (P = 0.008). Among men who developed ED during the follow up, all the QoL measures showed a deterioration, reaching statistical significance for physical functioning (P = 0.04), the physical component summary measure (P = 0.018), and quality of sexual life (P < 0.0001).

Patterns of QoL measures from 24 months before the onset of ED to 18 months after the onset of ED are displayed in Fig. 1. For all the SF-36 dimensions, a deterioration in QoL seems to precede the development of ED. In particular, in looking at the physical and mental components summary measures, the deterioration in the physical domain seems to precede by 6 months the decrease in the psychological well-being. The onset of ED is clearly associated with a further decrease in all the scores, which reach the lowest level concomitantly with its occurrence. Similarly, a worsening of depressive symptoms precedes the onset of ED, reaches its highest level concomitantly with it, and tends to plateau thereafter. As expected, erectile problems are associated with a steep decline in the quality of sexual life.

Multilevel models confirmed that no changes in QoL measures were detected during 3 years in men without ED, with the only exception being a marginally significant improvement in the social functioning SF-36 subscale (Table 3).

Among patients with ED at baseline, a worsening in all SF-36 scales was observed, even though statistical significance was reached for physical functioning only. The severity of depressive symptoms also slightly increased. On the other hand, the quality of sexual life score tended to improve (Table 3).

Among the patients who developed ED during the study, this condition was associated with a marked worsening in the physical functioning, general health perception, and social functioning SF-36 subscales as well as in the summary physical component score. The development of ED was also associated with a highly significant increase in depressive symptoms and a marked decrease in quality of sexual life (Table 3).

Among the other variables investigated, the severity of diabetes and its complications as summarized by the TIBI and the presence of CVD represented the strongest predictors of decline in all the scales. Low levels of school education and older age also predicted a worsening in the physical components of SF-36 (Table 3).

A few cross-sectional studies have described the association between the presence of ED and poorer QoL (1–5); nevertheless, no long-term, longitudinal evaluation of the impact of this condition on physical and psychological well-being is available. We describe for the first time changes in QoL occurring over 3 years in men with type 2 diabetes and ED and the deterioration in QoL subsequent to the development of ED.

In our study, QoL remained substantially unchanged among patients without erectile problems, whereas men with ED at baseline showed a significant deterioration in physical functioning. This finding can be related to the more severe clinical conditions of these patients, who show a markedly higher prevalence of micro- and macrovascular complications, as well as significantly older age. It is interesting to note that men with ED at baseline showed a statistically significant improvement in the quality of their sexual life. A noteworthy occurrence is that sildenafil became available on the market in Italy in 1998, concomitantly with the collection of the baseline data for our study. Therefore, although we do not have information about the use of this drug, it is reasonable to assume that such an improvement may be at least partially related to the availability of new effective oral treatments for ED.

The study offered a unique opportunity to evaluate QoL in patients with type 2 diabetes before and after the onset of ED. From a clinical point of view, men who developed ED during the follow-up had more severe clinical conditions at baseline compared with those without ED but very similar to those who had already reported erectile problems at study entry. These findings suggest that the presence of ED should be regularly investigated in patients with type 2 diabetes of longer duration, particularly when associated with micro- and macrovascular complications.

Patterns of QoL scores before and after the onset of ED suggest that a deterioration in physical well-being, followed by a worsening in psychological well-being, precede the development of sexual problems, thus suggesting an interplay between clinical and psychological factors in determining ED. Such a decline in QoL was not attributable to the incidence of new CVD events; in fact, only 8 of 192 patients who developed ED during the study also experienced a CVD event before ED onset. An alternative explanation for these findings could be represented by the occurrence of subtle pathological changes affecting the biopsychosocial functioning of the patient before manifestation of objective signs.

Erectile problems further deteriorate a patient’s health perception: for all the aspects investigated a worse score was reached concomitantly with the reporting of erectile problems. These findings were confirmed by multilevel analyses suggesting a greater impact of ED on physical functioning, depressive symptoms, general health perception, and social functioning. As expected, the dimension of QoL more seriously affected was represented by quality of sexual life, showing a dramatic decline as a consequence of ED onset.

Our data underline the importance of monitoring patients’ physical and emotional well-being: a deterioration in these aspects of QoL can represent an alarm bell for the development of sexual problems that will further contribute to worsen subjective health perception. Because patients could be reluctant to discuss their sexual problems, physicians should actively investigate these aspects in the light of the availability of effective treatments. In this regard, several studies have shown the positive effects of therapy on different aspects of QoL (14–17).

Two potential methodological limitations of our study need to be discussed. The presence of ED was based on patient self-report, without any attempt to clinically confirm the diagnosis. Nevertheless, subjective evaluation of the individual’s erection and satisfaction for sexual life are more likely to influence psychological well-being rather than the objective evaluation of the degree of ED. Second, we had no information on the use of treatment for ED after its diagnosis. Therefore, QoL scores after the onset of ED could have been at least partially influenced by such therapies and the impact of ED could be even greater than that documented.

In summary, this longitudinal study documents for the first time the impact of the onset of ED on several aspects of QoL in patients with type 2 diabetes. The study also shows that QoL tended to further decrease during 3 years in patients with ED at baseline, but not in those without this condition.

Giorgia De Berardis, MScPharmChem; Fabio Pellegrini, MScStat; Monica Franciosi, MScBiolS; Maurizio Belfiglio, MD; Barbara Di Nardo, HSDip; Sheldon Greenfield, MD; Sherrie H. Kaplan, PhD, MPH; Maria C.E. Rossi, MScPharmChem; Michele Sacco, MD; Gianni Tognoni, MD; Miriam Valentini, MD; Antonio Nicolucci, MD.

Vittorio Caimi, MD; Fabio Capani, MD; Andrea Corsi, MD; Roberto Della Vedova, MD; Massimo Massi Benedetti, MD; Antonio Nicolucci, MD; Claudio Taboga, MD; Massimo Tombesi, MD; Giacomo Vespasiani, MD.

P. Maresca, F. Malvicino, Alessandria; A. Corsi, E. Torre, P. Ponzani, F. Menozzi, Arenzano (GE); L. Gentile, Asti; P. Di Berardino, Atri (TE); P. Dell’Aversana, Aversa (CE); T. Savino, Bari; G. Amore, Bassano Del Grappa (VI); F. Travaglino, G. Morone, Biella; N. Pinna, Borgosesia (VC); M.A. Poli, Bovolone (VR); A.M. Sanna, L. Carboni, M. Brundu, Cagliari; F. Vancheri, A. Burgio, Caltanissetta; M. De Fini, Carbonara (BA); L. Vincis, G. Renier, Carbonia (CA); G. Bargero, A. Caramellino, G. Ghezzo, E. Venturi, Casale Monferrato (AL); J. Grosso, Castel di Sangro (AQ); G. De Simone, S. Gentile, I. Gaeta, Castellammare di Stabia (NA); L. Panzolato, Castiglione delle Stiviere (MN); V. Trinelli, Ciriè (TO); C. Campanelli, R. Norgiolini, Città di Castello (PG); R. Pastorelli, S. Fiore, Colleferro (RM); C. Cazzalini, F. Menozzi, S. Inzoli, C. Valsecchi, Crema (CR); G. Borretta, G. Magro, F. Cesario, A. Piovetan, M. Procopio, Cuneo; G. De Giuli, Darfo Boario Terme (BS); G. Marelli, L. Bellato, Desio (MI); D. Richini, Esine (BS); A. Muscogiuri, F. Tanzarella, Francavilla Fontana (BR); E. Santilli, G.S. Versace, Frascati (RM); G. Morandi, C. Mazzi, Gallarate (VA); P. Melga, V. Cheli, A. De Pascale, Genova; V. Majellaro, Giovinazzo (BA); E. D’Ugo, Gissi (CH); A. Morea, Isola della Scala (VR); L. De Giorgio, R. Lecis, La Spezia; M. Pupillo, Lanciano (CH); M. Nuzzo, G. Formoso, D. Cosi, Lecce; A. Caldonazzo, Leno (BS); I. Lorenti, Lentini (SR); R. Guarneri, I. Guarneri, Locri (RC); G. Maolo, M. Giovagnetti, Macerata; F. Saggiani, G. Pascal, E. Dina, Mantova; L. Sciangula, P. De Patre, F. Azzalini, C. Mauri, C. Roncoroni, E. Banfi, Mariano Comense (CO); A. Venezia, R. Morea, Matera; P. Pata, T. Mancuso, A. Cozzolino, C. De Francesco, Messina; S. Negri, G. Adda, A. Zocca, A. G. Perdomini, G. L. Pizzi, Milano; S. Gentile, G. Guarino, B. Oliviero, S. Turco, A. Fischetti, M. R. Marino, G. Di Giovanni, G. Borrelli, Napoli; G. Torchio, P. Palumbo, Paderno Dugnano (MI); M.L. Belotti, Palazzolo sull’Oglio (BS); V. Provenzano,S. Imparato, V. Aiello, M. Fleres, Partinico (PA); S. Bazzano, G. Nosetti, Pavia; E. Antonacci, Penne (PE); F. Capani, E. Vitacolonna, E. Ciccarone, R. Ciancaglini, G. Di Martino, G. La Penna, Pescara; F. Galeone, Pescia (PT); U. De Joannon, M. Bianco, d. Zavaroni, Piacenza; C. Ruffino, Pietra Ligure (SV); E. Bassi, R. Ghirardi, Pieve di Coriano (MN); G. De Simone, M. Riccio, Portici (NA); A. Bianchi, R. Dagani, Rho (MI); A. Urbani, S. Leotta, G. Ceccarelli, A. Baldelli, A. Napoli, M. Liguori, O. Laurenti, G. De Mattia, Roma; G. Monesi, F. Mollo, R. Manunta, G. Lisato, F. Beretta, L. Bellinetti, P. Bordon, Rovigo; E. Bagolin, San Donà di Piave (VE); L. Clementi, G. Vespasiani, San Benedetto del Tronto (AP); E. Del Vecchio, F. Orio, D. Caggiano, M. Tenuta, Salerno; G.M. Arca, V. Scardaccio, Sassari; A. Diana, G. Montegrosso, S. Grottoli, M. Tati, M.P. Della Valle, Savigliano (CN); M.B. Diodati, A. Tritapepe, Sulmona (AQ); C. Coppola, M. Bosi, Suzzara (MN); M. Magno, E. Scarpa, Taranto; E. Lattanzi, G. Damiani, D. Di Michele, a. Fava, E. Di Pietro, M. Brancali, Teramo; M. Veglio, M. D’Andrea, A. Grassi, A. Mormile, A. Bruno, E. Pisu, V. Tagliaferro, P. Passera, M. Trento, Torino; A. Margiotta, Tradate (VA); A. Bossi, Treviglio (BG); C. Taboga, S. Mreule, C. Noacco, F. Colucci, L. Tonutti, Udine; S. Sposito, Velletri (RM); A.R. Bogazzi, Venaria (TO); E. Moro, C. Zanbon, M. Pais, G. Bittolo Bon, A. Sfriso, Venezia; M.F. Francesconi, G. Erle, Vicenza.

D. Sabbi, Arquata Scrivia (AL); L. Lippa, Avezzano (AQ); M. Casassa Vigna, Balangero (TO); A. D’Alessandro, Bari; N. Caniglia, Barrea (AQ); G. Omati, Bussero (MI); G. Danti, Buttapietra (VR); L. Pascali, Camerano (AN); G. Ragazzi, Camisano Vicentino (VI); E. Di Febo E, Carsoli (AQ); L. Ballarini, Castel D’Azzano (VR); P. Tonello, Castelgomberto (VI); V. Capilupi, Catanzaro; D. De Giorgi, Cavallino (LE); C. Spiezio, Ciriè (TO); F. Della Cagnoletta, Colorina (SO); E. Beretta, Concorezzo (MI); M.T. Nepote Fus, T. Rapacciuolo, Corio (TO); A. Metrucci, Cutrofiano (LE); A. Veldorale, Druento (TO); E. Ioverno, G. Visentin, Dueville (VI); L. Bellino, Firenze; E. Brizio, Fossano (CN); G. Frapporti, Fumane (VR); R. Della Vedova, Gradisca d’Isonzo (GO); F. Gesualdi, Latronico (PZ); E. Mola, D. Fiume, Lecce; M. Falcoz, Loira (TV); G. Martinelli, Lovere (BG); M. Tombesi, L. Caraceni, Macerata; E. Di Giovanbattista, Magnano in Riviera (UD); T. Ermacora, Maiano (UD); A. Gualtiero, Malo (VI); F. Morelli, G. Capozza, Matera; M. Musso, Mathi (TO); S. Pagliani, P. Longoni, Milano; V. Caimi, Riva MG, M. Bosisio, Monza (MI); L. Bertini, Monzuno (BO); R. Barra, F.M. D’Alessandro, R. Alano, Napoli; G. Mezzasalma, Nole Canavese (TO); L. Barberio, Paganica (AQ); F. Petrona Baviera, Palermo; C. De Matteis, Paola (CS); B. Anglano, Verona; P. Scarpolini, Pescantina (VR); M. Milano, S. Bernabè, Pianezza (TO); S. Filippi, Pontremoli (MS); C. Tosetti, Porretta Terme (BO); P. Dorato, Pozzuoli (NA); A. Moro, Preganziol (TV); La Terra Bella B, Ragusa; M. Marziani, Reggio Emilia; S. Burzacca, Rivalta Di Torino (TO); A. Zamboni, Ro (FE); F. Saliceti, P.L. Bartoletti, L. Spalletta, Roma; L. Bonicatto, San Francesco al Campo (TO); A. Catalano, San Leucio del Sannio (BN); L. Crapesi, San Lorenzo Isontino (GO); G. Mattana, San Sperate (CA); M.L. Agnolio, Sandrigo (VI); G. Piazza, Santorso (VI); G. Lattuada, Saronno (VA); L. Gambarelli, Scandiano (RE); A. Bussotti, Sesto Fiorentino (FI); A. Pinsuti, Sinalunga (SI); L. Signorati, Sommacampagna (VR); V. Baggi, Sordio (LO); R. Riundi, Sumirago (VA); M. Uberti, A.R. Mondazzi, R. Massaro, M. Botto Micca, Torino; D. Massignani, Valdagno (VI); F. Gazzetta, F. Bianchetti, D. Molla, Varese; R. Marino, Venaria (TO); T. Galopin, G. Pettenella, E. Bonollo, Verona; P.F. Luvisi, Viareggio (LU); A. Frigo, G. Cabri, C. Simionato, Vicenza; S. Bevilacqua, L. Longhi, Viterbo; G. Dezio, Vittoria (RG).

This study was supported by Pfizer Italiana S.p.A and partially supported by Italian “Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR)” (DM 623/96-2002).

The authors thank Sonia Ferrari and Marco Piaggione for their technical support.