We appreciate the comments by Rigalleau et al. (1) regarding our article (2) and agree that tissular accumulation of advanced glycation end products (AGEs) as an alternative mechanism that may contribute to the reduced incidence of cancer after the remission of diabetes is interesting.
We thank the authors for sharing their data on accumulation of AGEs in patients with obesity and the association with higher risk of incident cancer in those with the most arbitrary units of skin autofluorescence of AGEs. Indeed, it would be interesting to analyze the levels of soluble receptor for advanced glycation end product concentrations during long-term follow-up periods after bariatric surgery; however, at present no such data are available for Swedish Obese Subjects (SOS) study participants.
As suggested by the authors, we performed a more detailed analysis on incident cancer in groups of patients with long- versus short-term duration of diabetes remission after bariatric surgery. In this analysis (note that only patients with known diabetes status at both 2 and 10 years were included in this analysis), we found that the incidence rate (IR) per 1,000 person-years in the group of surgery patients with diabetes remission at both 2 and 10 years (N = 81) was 6.3 (95% CI 3.5–11.3, 11 events), which should be compared with the IR in the group of surgery patients with diabetes remission at 2 years but where diabetes had relapsed at 10 years (N = 97) (IR/1,000 person-years = 11.5 [95% CI 7.7–17.3, 23 events]). Thus, the IR in patients whose diabetes only remitted at 2 years following surgery was similar to that previously reported for all SOS study participants who were not in remission at 10 years (IR/1,000 person-years = 11.4 [95% CI 9.1–14.3]) (2). These results further support the importance of durable diabetes remission for cancer risk reduction in patients with obesity and diabetes, but to confirm these results and uncover the underlying mechanisms, future studies are needed.
Acknowledgments. The authors thank the staff members at 480 primary health care centers and 25 surgical departments in Sweden who participated in the SOS study.
Funding. Research reported in this publication was supported by the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG-717881 and ALFGBG-717891), the Swedish Research Council (2017-01707), the Novo Nordisk Foundation (NNF 19OC0057184), the Swedish Heart-Lung Foundation (20180410), and the Swedish Diabetes Foundation (2019-417), The Assar Gabrielsson Foundation (FB2019-41).
The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Duality of Interest. L.M.S.C. has received consulting fees from Johnson & Johnson. No other potential conflicts of interests relevant to this article were reported.