Elevated inflammation supra-additively promotes the progression from prediabetes to diabetes: a prospective cohort study

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Background: Factors impacting on the conversion of prediabetes to diabetes or normoglycemia remain unclear. This study aimed to investigate the role of subclinical inflammation, assessed by high-sensitivity C-reactive protein (hsCRP), in the progression to diabetes from prediabetes, assessed by impaired fasting glucose (IFG). Methods: Time-to-event survival analyses were conducted among 82 475 participants without diabetes from Kailuan Study (a real-life prospective cohort in China) to access the isolated and joint effect of hsCRP and IFG on diabetes risk, and quantify their relative contribution to incident diabetes. Results: Over a median 11-year follow-up, 14 215 diabetes cases were recorded. IFG and hsCRP independently and jointly increased diabetes risk. Diabetes incidence was higher in those with elevated inflammation (hsCRP≥2 mg/L: 90.45 vs. 66.76 per 1000 person-years). The joint effect risk (hazard ratios (HR) = 4.96; 95% confidence interval (CI) = 4.66-5.28) exceeded the sum of individual risks (HR = 4.29; 95% CI = 4.09-4.49 for IFG and HR = 1.11; 95% CI = 1.06-1.16 for elevated inflammation), with a relative excess risk due to interaction of 0.56 (95% CI = 0.23-0.89). Attributable proportions were 83.08% for IFG, 2.78% for hsCRP, and 14.14% for their interaction. The joint risks and the additive interaction were significant in both men and women, and were more pronounced among individuals aged <60 years than those aged ≥60 years. Conclusions: Elevated inflammation synergistically amplifies diabetes risk in prediabetes among Chinese adults, particularly in those <60 years.

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