Changes in Fasting Plasma Glucose and Risk of Mortality Events for Individuals without Diabetes over Two Decades of Follow-up: a Pooled Cohort Analysis

Abstract Background: To assess the gender-specific impact of 3-year changes in fasting plasma glucose (FPG) status on the risk of all-cause, cardiovascular (CV), and cancer mortality in individuals without type 2 diabetes during an 18-year follow-up. Methods: The study population included 14,378 participants aged 30-60 years (8272 women) from three population-based cohort studies, including Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Tehran Lipid and Glucose Study. Subjects were classified into six categories based on the approximately three-year changes in FPG status: 1) normal FPG (NFG) to NFG (NFG-NFG, reference category); 2) NFG-impaired fasting glucose (IFG, i.e., 126> FPG ≥100 mg/dl); 3) NFG-type 2 diabetes (T2DM); 4) IFG-NFG; 5) IFG-IFG; 6) IFG-T2DM. Multivariable stratified Cox regression, adjusting for age, body mass index (BMI), BMI-Change, smoking status, hypertension, and hypercholesterolemia, was used to estimate hazard ratios (HRs [95% CI]) for all-cause and cause-specific mortality events. Women-to-men ratios of HRs (RHRs) for each category were also estimated. Results: During follow-up, 2362 incidences of all-cause mortality were recorded. Among women, all categories of FPG change, excluding IFG-NFG (HR, 95% CI; 1.24 [0.98–1.57], p-value=0.07), were associated with a higher risk of all-cause mortality compared to the NFG-NFG category. Moreover, women in IFG-T2DM (2.21 [1.42–3.44]) group were at increased risk for CV mortality. We also found that women in NFG-IFG (1.52 [1.20–1.91]), NFG-T2DM (2.90 [1.52–5.51]), and IFG-IFG (1.30 [1.02–1.66]) categories had a higher risk for cancer mortality. However, among men, a higher risk of all-cause mortality was found for only two groups of NFG-T2DM (1.78 [1.15–2.74]) and IFG-T2DM (1.34 [1.04–1.72]). Women with IFG-IFG had a 24% higher risk for all-cause mortality events than their men counterparts with the same condition (RHR; 1.24 [1.01–1.54]). Conclusion: In women, the IFG status, whether as incident, persistent, or converted to T2DM, had a higher risk for mortality events; however, among men, only conversion to T2DM conferred an excess risk of all-cause mortality.