Glucose tolerance phenotypes and risks of incident first-ever stroke and all-cause mortality in low-income rural Chinese adults: a population-based prospective cohort study.

Background and objective: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are common intermediate hyperglycaemic states, yet most cohorts have compared diabetes with non-diabetes, or have relied on fasting glucose alone, so the stroke risk gradient across the full glucose tolerance spectrum and the relative prognostic value of fasting versus postload glycaemia remain unresolved. Evidence is particularly scarce for low-income rural Chinese populations, in whom vascular risk factors cluster while chronic-disease management and screening resources are limited. This study aimed to investigate the associations of glucose tolerance status with incident first-ever post-baseline stroke and all-cause mortality among low-income rural adults in China. Methods: This population-based prospective cohort study included 2,087 adults from a low-income rural community in northern China who underwent a baseline examination including a 75-g oral glucose tolerance test (OGTT) in 2019. Among them, 2,057 participants with valid baseline examination dates were included in the time-to-event analyses, contributing 13,074.9 person-years for stroke and 13,477.4 person-years for mortality over a mean follow-up of 6.4 years. Baseline glucose tolerance status was classified as normal glucose tolerance (NGT), IFG, IGT, or diabetes according to the WHO/IDF criteria. Incident first-ever post-baseline stroke was defined as the first stroke event occurring after the 2019 baseline examination; participants with a stroke before baseline were excluded from this analysis, and all-cause mortality was recorded during follow-up. Incidence rates were calculated per 1,000 person-years and were additionally standardised for age and sex by the direct method. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. The primary multivariable model (Model 2) was adjusted for sex, age group, smoking, drinking and eGFR; metabolic syndrome was added only in Model 3 and examined separately, because it shares glycaemic components with the exposure. In addition, fasting glucose and 2-h postload glucose were analysed as continuous variables in separate models, so that fasting and postload glycaemia could be compared without inducing collinearity. Proportional hazards were assessed using scaled Schoenfeld residuals, and multiple-imputation, Fine-Gray competing-risk and prespecified subgroup analyses were performed as sensitivity analyses. Results: During follow-up, 121 participants developed incident first-ever post-baseline stroke and 68 died from any cause, corresponding to overall incidence rates of 9.25 and 5.05 per 1,000 person-years, respectively. For incident stroke, the incidence rates were 7.55, 5.40, 12.74, and 14.06 per 1,000 person-years in the NGT (n = 1,324; 63.4%), IFG (n = 86; 4.1%), IGT (n = 449; 21.5%), and diabetes (n = 228; 10.9%) groups, respectively; for all-cause mortality the corresponding rates were 4.68, 1.77, 6.27 and 6.05 per 1,000 person-years. In crude analyses, both IGT (HR 1.69, 95% CI 1.11-2.55, *P* = 0.013) and diabetes (HR 1.85, 95% CI 1.12-3.06, *P* = 0.016) were associated with a higher risk of incident first-ever stroke compared with NGT. In the primary multivariable model (Model 2), both IGT (HR 1.58, 95% CI 1.03-2.41, *P* = 0.036) and diabetes (HR 1.69, 95% CI 1.02-2.81, *P* = 0.043) remained associated with incident stroke, whereas IFG did not (HR 0.78, 95% CI 0.25-2.51, *P* = 0.682). Adding metabolic syndrome (Model 3) attenuated both estimates and rendered diabetes non-significant (IGT: HR 1.55, 95% CI 1.01-2.39, *P* = 0.046; diabetes: HR 1.63, 95% CI 0.96-2.79, *P* = 0.071). No glucose tolerance subtype was significantly associated with all-cause mortality in any model. In continuous analyses modelled separately, both fasting glucose (HR 1.18 per 1 mmol/L, 95% CI 1.01-1.38, *P* = 0.035) and 2-h postload glucose (HR 1.07 per 1 mmol/L, 95% CI 1.02-1.13, *P* = 0.008) were associated with incident stroke; per standard deviation the postload association was the stronger of the two (HR 1.23, 95% CI 1.05-1.42 versus HR 1.17, 95% CI 1.01-1.35). Neither measure was associated with mortality. Conclusion: Three conclusions follow. First, in this specific setting - a low-income rural Chinese community with clustered vascular risk factors and limited screening capacity - both IGT and diabetes were associated with an increased risk of incident first-ever stroke, whereas isolated IFG was not. Second, postload glycaemia carried more prognostic information for stroke than fasting glycaemia: the postload association was the stronger of the two per standard deviation, and only the postload phenotype (IGT) showed an excess risk in the categorical analysis, while the continuous fasting association appeared to be driven largely by participants in the diabetes range rather than by isolated fasting hyperglycaemia. Third, for grassroots public-health practice these findings identify IGT as a candidate phenotype for earlier vascular risk assessment; whether adding postload measurement to existing screening improves outcomes remains to be tested directly.