Trajectories of type 2 diabetes and cancer in 330 000 individuals with prediabetes: 20-year observational study in England.
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BACKGROUND: Higher than normal glucose concentrations have been linked to an increased risk of cancer. We aimed to describe the disease trajectories from prediabetes to cancer, accounting for the possible conversion to type 2 diabetes and risk of death. METHODS: We used the Clinical Practice Research Datalink primary care records linked to hospital and mortality records to identify individuals aged 18-100 years with newly diagnosed prediabetes between Jan 1, 1998, and Nov 30, 2018, in England. Individuals were followed from the diagnosis of prediabetes until death or Nov 30, 2018, with two intermediate outcomes: type 2 diabetes and cancer. In a multistate model, we estimated state occupancy probabilities and lengths of stay (sojourn times) across eight states and seven transitions (eg, one transition from the prediabetes state to the cancer state; or three transitions from the prediabetes state to the type 2 diabetes, cancer, and death state). FINDINGS: During a median follow-up of 7·7 years, 163 782 transitions occurred in 328 049 individuals. In both women and men, cancer incidence rates were greater in older individuals (aged ≥75 years at prediabetes diagnosis) and only marginally higher in those who developed type 2 diabetes versus those with prediabetes (over 10 years, the largest differences were 4·1 more cases per 1000 person-years in women and 4·8 more cases per 1000 person-years in men). 10 years after the diagnosis of prediabetes, the probability of remaining in the prediabetes state ranged from 23·2% (men aged ≥75 years at diagnosis) to 72·1% (men aged <55 years), the probability of death following prediabetes ranged from 1·2% (women aged <55 years) to 38·7% (women aged ≥75 years), the probability of developing type 2 diabetes and remaining in this state ranged from 7·9% (men aged ≥75 years) to 24·0% (women aged <55 years), and the probability of developing cancer and remaining in this state ranged from 1·9% (men aged <55 years) to 7·8% (men aged ≥65 to <75 years) in men and women. During the 10 years following the diagnosis of prediabetes, individuals spent between 5·34 years (men aged ≥75 years at diagnosis) to 8·34 years (men aged <55 years) in the prediabetes state. BMI, smoking, socioeconomic status, and ethnicity were associated with occupancy probabilities and sojourn times. INTERPRETATION: The trajectories of type 2 diabetes and cancer following a diagnosis of prediabetes varied substantially by age at prediabetes diagnosis and, to a lesser extent, other sociodemographic and lifestyle factors, with most younger individuals (aged <55 years) remaining in the prediabetes state. Strategies to improve the prevention and early identification of type 2 diabetes and cancer in individuals with prediabetes should be tailored to the age at which prediabetes is diagnosed. FUNDING: National Institute for Health and Care Research (NIHR) Applied Research Collaboration, East Midlands, NIHR Leicester British Retail Consortium, Hope Against Cancer.