The declining insulinogenic index correlates with inflammation and metabolic dysregulation in non-obese individuals assessed by blood gene expression

[Display omitted] •Blood gene expression analyses for the same 96 participants in 2008 and 2016.•Blood gene expression correlates with insulinogenic index (IGI) variations.•Declining IGI over 8 years correlates with metabolic dysregulation and inflammation.•Individuals with minor change in IGI featured homeostatic and regenerative response.•Gene expression useful for identifying prognostic biomarkers for declining IGI. Diabetes onset is difficult to predict. Since decreased insulinogenic index (IGI) is observed in prediabetes, and blood gene expression correlates with insulin secretion, candidate biomarkers can be identified. We collected blood from 96 participants (54 males, 42 females) in 2008 (age: 52.5 years) and 2016 for clinical and gene expression analyses. IGI was derived from values of insulin and glucose at fasting and at 30 min post-OGTT. Two subgroups were identified based on IGI variation: “Minor change in IGI” group with absolute value variation between –0.05 and +0.05, and “Decrease in IGI” group with a variation between –20 and –0.05. Following the comparison of “Minor change in IGI” and “Decrease in IGI” groups at time 0 (2008), we identified 77 genes correlating with declining IGI, related to response to lipid, carbohydrate, and hormone metabolism, response to stress and DNA metabolic processes. Over the eight years, genes correlating to declining IGI were related to inflammation, metabolic and hormonal dysregulation. Individuals with minor change in IGI, instead, featured homeostatic and regenerative responses. By blood gene expression analysis of non-obese individuals, we identified potential gene biomarkers correlating to declining IGI, associated to a pathophysiology of inflammation and metabolic dysregulation.