Glycoprotein acetyls response to a mixed meal is associated with increased insulin resistance and risk of type 2 diabetes in a middle-aged population

Background & aims Systemic inflammation increases the risk of type 2 diabetes (T2D). It remains unclear whether the inflammatory meal response identifies other people at risk of T2D than fasting levels alone. We aimed to examine associations between the meal response of glycoprotein acetyls (GlycA) with insulin resistance and incident type 2 diabetes. Methods In 5755 middle-aged participants (47 % men) without pre-existing diabetes GlycA was measured after an overnight fast and 150 min after a liquid mixed meal (400 mL, 600 kCal, 16 percent of energy (En%) derived from protein, 50 En% carbohydrates, and 34 En% fat). With linear regression, we examined associations between the GlycA meal response and measures of insulin resistance. With Cox regression analyses, we examined associations between the GlycA meal response and incident type 2 diabetes, adjusted for demography and lifestyle factors. Results In our population, mean (SD) fasting GlycA was 1.28 (0.21) mmol/L and mean GlycA meal response was 0.16 (0.13) mmol/L, and these were weakly correlated (ρ = 0.19). After adjustment for confounding, insulin resistance (HOMA-IR) was 1.11-fold higher (95 % CI: 1.09; 1.13) per SD GlycA meal response. During a median follow-up of 6.7 years, 287 participants developed T2D. Per SD GlycA meal response, the adjusted hazard ratio of incident type 2 diabetes was 1.12 (95 % CI: 1.00; 1.26). Conclusion In this middle-aged population with overweight, those with a high GlycA meal response, including those with low fasting GlycA, had an increased risk of diabetes. A high inflammatory meal response shows promise to identify other people at risk of T2D than fasting levels alone. This risk group may benefit from prevention by precision nutrition to reduce the inflammatory meal response.