The study's goal is to assess circulating metabolites and their correlations with coronary heart disease (CHD) in both men and women, regardless of glycaemic status. 

The metabolomic data (amino acids, glycolysis, ketone bodies, inflammation, fluid balance, fatty acids, lipids, and lipoproteins) of 95,108 CHD-free UK Biobank participants were used in the investigation. They examined the association between sex and metabolites (log) in newly diagnosed T2D (diagnosis<2 yrs from baseline), prediabetes (A1c 5.7-6.5%), and euglycemia using linear regressions accounting for age, race, Deprivation Index, income, smoking, obesity, and antilipidemics, antihypertensive and antidiabetes medications. We utilized Cox model to examine the link between metabolites and CHD risk by sex, adjusted for the same variables and menopausal state. Each analysis was FDR adjusted. 

There were 1328 cases of new T2DM, 6204 cases of prediabetes, and 87,576 cases of euglycemia identified. The levels of glycoprotein acetyls (GlycA, inflammation), fatty acids (total, polyunsaturated, saturated fatty acids [SFA]), lipids (phosphoglycerides, cholines, sphingomyelins, phospholipids), atherogenic lipoproteins (total cholesterol, non-HDL-c, remnant-c, LDL-c, cholesteryl esters, ApoB) were more in women as compared to men throughout glycaemic statuses (pinteraction<.05). This was specifically true in T2DM (ptrend< .05). Across all glycemic levels, men exhibited higher amounts of creatinine and albumin (ptrend< .05). Men showed greater creatinine and albumin levels with varying blood sugar levels (ptrend<.05). In a 10-year follow-up, women with T2D had greater GlycA (W HR 16.1, 95%CI 2.1-137.8 vs M 0.5, 0.1-1.7), SFA (W 4.5, 1.5-13.8 vs M 0.9, 0.5-2.8), TG/phosphoglycerides ratio (W 3.0, 1.4-6.8 vs M 1.3, 0.7-2.3), and total TG (W 2.5, 1.3-4.9 vs M 1.1, 0.7-1.7), but not men (pinteraction<.1).

It was shown that when glycaemic status increased, men's renal indicators were greater while in women's inflammatory, fatty acid, and atherogenic lipid markers were higher. Compared to males with T2DM, women with the T2D have a greater risk of CHD linked to GlycA, SFA, and TG.

152-OR: American Diabetes Association (ADA) 84th Scientific Sessions, 2024, 21- 24 June 2024, Orlando, Florida.