Progression from different blood glucose states to cardiovascular diseases: a prospective study based on multi-state model

Abstract Aims To quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cardiovascular death, and the effects of risk factors on the rates of transition. Methods and results We used data from the Jinchang Cohort of 42 585 adults aged 20–88 free of coronary heart disease (CHD) and stroke at baseline. A multistate model was applied for analysing the progression of CVD and its relation to various risk factors. During a median follow-up of 7 years, 7498 participants developed pre-diabetes, 2307 developed T2DM, 2499 developed CVD, and 324 died from CVD. Among 15 postulated transitions, transition from comorbid CHD and stroke to cardiovascular death had the highest rate (157.21/1000 person-years), followed by transition from stroke alone to cardiovascular death (69.31/1000 person-years) and transition from pre-diabetes to normoglycaemia (46.51/1000 person-years). Pre-diabetes had a sojourn time of 6.77 years, and controlling weight, blood lipids, blood pressure, and uric acid within normal limits may promote reversion to normoglycaemia. Among transitions to CHD alone and stroke alone, transition from T2DM had the highest rate (12.21/1000 and 12.16/1000 person-years), followed by transition from pre-diabetes (6.81/1000 and 4.93/1000 person-years) and normoglycaemia (3.28/1000 and 2.39/1000 person-years). Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions. Conclusion Pre-diabetes was the optimal intervention stage in the disease trajectory. The derived transition rates, sojourn time, and influence factors could provide scientific support for the primary prevention of both T2DM and CVD. Lay Summary Former single-outcome studies on the relationship between glycaemia and cardiovascular disease (CVD) may ignore the complexity and multi-transformations across the multiple stages from normoglycaemia to CVD in real-world setting. We aimed to quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes, CVD, and cardiovascular death. Pre-diabetes was the optimal intervention stage in the disease trajectory. Transitions from CVD to death had much higher rates than other transitions. Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemi