Relationship between type 2 diabetes mellitus and markers of cutaneous melanoma aggressiveness: an observational multicentric study in 443 patients with melanoma*
Eduardo Nagore, Miguel Ángel Martínez‐García, José Daniel Gómez-Olivas, Esperanza Manrique‐Silva, Antonio Martorell, José Bañuls, Cristina Carrera, Pablo L. Ortiz‐Romero, Jesús Gardeazábal, Aram Boada, Esther de Eusebio, Eusebi Chiner, Cristina González, Amalia Pérez‐Gil, D. Cullen, M. Formigón, Blanca de Unamuno, Cristina Navarro‐Soriano, Alfonso Muriel, David Gozal
Abstract
Background Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are under way to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis. Objectives To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma. Methods We conducted a cross-sectional multicentric study in 443 patients diagnosed with cutaneous melanoma. At diagnosis, all patients completed a standardized protocol, and a fasting blood sample was extracted to analyse their glucose levels, glycated haemoglobin concentration and markers of systemic inflammation. Melanoma characteristics and aggressiveness factors [Breslow thickness, ulceration, tumour mitotic rate (TMR), sentinel lymph node (SLN) involvement and tumour stage] were also recorded. Results The mean (SD) age of the patients was 55·98 (15·3) years and 50·6% were male. The median Breslow thickness was 0·85 mm. In total, 48 (10·8%) patients were diagnosed with T2DM and this finding was associated with a Breslow thickness > 2 mm [odds ratio (OR) 2·6, 95% confidence interval (CI) 1·4–4·9; P = 0·004)] and > 4 mm (OR 3·6, 95% CI 1·7–7·9; P = 0·001), TMR > 5 per mm2 (OR 4·5, 95% CI 1·4–13·7; P = 0·009), SLN involvement (OR 2·3, 95% CI 1–5·7; P = 0·038) and tumour stages III–IV (vs. I–II) (OR 3·4, 95% CI 1·6–7·4; P = 0·002), after adjusting for age, sex, obesity, alcohol intake and smoking habits. No significant associations emerged between glycated haemoglobin levels, metformin treatment and melanoma aggressiveness. Conclusions T2DM, rather than glycaemic control and metformin treatment, is associated with increased cutaneous melanoma aggressiveness at diagnosis.