Feed

4-Hydroxyproline, a product of collagen turnover generated through prolyl hydroxylation, has been implicated in metabolic regulation. While previous studies have associated circulating proline with diabetes, the relationship between 4-hydroxyproline and diabetes remains unclear.

We conducted a cross-sectional analysis of 796 adults aged 35-74 years from Changshu, eastern China. Plasma 4-hydroxyproline levels were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Higher plasma 4-hydroxyproline levels were associated with increased odds of diabetes after multivariable adjustment (per SD increase: OR = 1.35, 95% CI: 1.10-1.66; p = 0.004). Participants in the highest quartile had higher odds of diabetes than those in the lowest quartile (Q4 vs. Q1: OR = 1.86, 95% CI: 1.01-3.47; p for trend = 0.006). The associations remained materially unchanged after excluding insulin users, individuals with diabetes-related complications, and those using antidiabetic medication. Further adjustment for dietary intake and proline did not materially alter the results.

Higher plasma 4-hydroxyproline levels were associated with diabetes. Given the cross-sectional design, causality cannot be inferred, and reverse causation cannot be excluded. Prospective studies are needed to confirm these findings.