Endocrine Abstracts

Background: There are differences in the development of diabetic nephropathy (DN) between men and women but the underlying molecular mechanisms are unknown. The urinary proteome may contain sex-specific biomarkers and thereby identify differentially regulated pathways to DN in men and women.

Method: Urine samples were obtained from 157 patients with type 2 diabetes (age, 61 (29–71) years; 120 men and 37 women), preserved renal function (eGFR, 88 ± 17 ml/min) and microalbuminuria (UAER, 85 [34;194] mg/24hrs). Peptidomic analysis was undertaken using capillary electrophoresis coupled to mass spectrometry. We compared individual urinary peptides between men and women.

Results: We detected 4914 individual peptides across all samples. Sex-specific differences were seen in expression of 343 (Chi squared, P < 0.05); with 86 and 257 peptides more common in men and women respectively. We then performed quantitative analysis of 196 peptides that were found in at least 25% of male or female subjects. Of these, 165 peptides were significantly (Mann-Whitney U-test, P < 0.05) differently expressed in urine; eight of these displayed a 10-fold difference between sexes at significance level of <0.001. Sex was the strongest determinant of abundance after adjustment for age, eGFR and UAER. In men, presence of Peptide 186095 was associated with lower UAER (P < 0.001), in women this was the case for Peptide 187114 (P = 0.024).

Conclusions: Of 4914 urinary peptides, 196 exhibit sex-specific regulation in a cohort of patients with early DN. Specific peptides are associated with albuminuria in men and women. These are derived from collagen alpha 1; alpha 1 antitrypsin; and membrane associated progesterone receptor component 1. Biological activity and predictive value of these peptides are unknown. Exploration of larger datasets is required to confirm these results and determine whether sex-specific regulation of urinary peptides explains differences in DN progression.