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

Diabetologia. 2026 Jun 5. doi: 10.1007/s00125-026-06758-7. Online ahead of print.

ABSTRACT

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.

PMID:42247170 | DOI:10.1007/s00125-026-06758-7