The impact of gender on urine C-peptide creatinine ratio interpretation

Background: Urinary C-peptide creatinine ratio (UCPCR) is a non-invasive and convenient way of assessing endogenous insulin production. Adjusting for urine creatinine levels allows for differences in urine concentration. Creatinine excretion is known to be higher in men due to gender differences in muscle mass. We investigated the impact of gender on UCPCR. Methods: One hundred and seventy-six subjects underwent a mixed meal tolerance test (MMTT). We looked at the relationship between UCPCR on urine C-peptide and creatinine excretion rates using timed post-meal urine samples. A further 415 subjects had two-hour post-meal UCPCR measurements in order to derive gender-specific percentiles for different diabetes subgroups and controls. Results: UCPCR was 1.48-fold higher in women (n = 78) than men (n = 98), median (interquartile range [IQR]): 1.88 (0.49-3.49) men versus 2.88 (1.58-4.91) nmol mmol(-1) women, P = 0.01. This reflects a gender difference in creatinine excretion rates (11.5 [8.3-13.7] men versus 8.2 [5.6-9.1] women mu mol min(-1) P < 0.001). C-peptide excretion rate was similar in men and women (19.8 [5.2-37.0] versus 22.1 [7.4-40.5] pmol min(-1), P = 0.7). UCPCR was higher in women in all subgroups defined by diabetes classification and treatment, except long-term type 1 diabetes in whom C-peptide secretion was minimal. Conclusions: Gender affects UCPCR, with higher values found in women. This results from lower urine creatinine reflecting gender differences in muscle mass. This necessitates gender-specific ranges for accurate interpretation of UCPCR results.