Early glycaemic exposure and cancer risk in people with newly diagnosed type 2 diabetes

Aims/hypothesis The aim of this study was to determine whether overall and time-specific patterns of hyperglycaemia, particularly soon after diagnosis, are associated with incident cancer in adults with newly diagnosed type 2 diabetes. Methods We retrospectively analysed a territory-wide cohort of 52,926 Hong Kong Chinese people with newly diagnosed type 2 diabetes. We examined cancer risk across groups of individuals classified according to their time-weighted mean HbA 1c over the entire follow-up period ( n =49,978) or during specific early exposure periods ( n =39,185). A weighted cumulative exposure model was used to determine the role of historical HbA 1c exposures in cancer development ( n =49,966). Results Among 49,978 individuals with newly diagnosed type 2 diabetes, 1758 cancer events occurred. Each 11 mmol/mol (1%) increase in time-weighted mean HbA 1c was associated with a 27% relative higher risk of cancer at any site (HR 1.27; 95% CI 1.20, 1.33). Within the first 2 years after diagnosis, a time-weighted mean HbA 1c ≥53 mmol/mol (≥7.0%) vs <53 mmol/mol (<7.0%) was associated with a 30–75% relative higher risk of cancer at any site, depending on the specific HbA 1c category, even after adjusting for subsequent HbA 1c . Longer durations of early exposure were associated with higher risk, reaching 51–213% in the first 5 years of exposure. Earlier high HbA 1c exposures contributed more strongly to cancer risk than later exposures. A 11 mmol/mol (1%) HbA 1c reduction at 1–2 years was associated with a 6% relative lower cancer risk over a hypothetical 10 year window (HR 0.94; 95% CI 0.91, 0.98), whereas reductions after 5 years showed no significant risk differences. Conclusions/interpretation Overall, hyperglycaemic exposure was associated with an elevated long-term cancer risk in type 2 diabetes. Notably, individuals who showed better glycaemic management soon after diagnosis exhibited a lower cancer risk than those whose glycaemic management improved later, despite comparable overall glycaemic burdens.