Elevation of erythrocyte creatine post-puberty unrelated to erythrocyte lifespan: Implications from the lack of correlation between HbA1c and erythrocyte creatine

Takahide Kokumai; Shigeru Suzuki; Satoru Takahashi; Toshika Okumiya; Masafumi Koga

doi:10.1016/j.cca.2025.120130

Elevation of erythrocyte creatine post-puberty unrelated to erythrocyte lifespan: Implications from the lack of correlation between HbA1c and erythrocyte creatine

Clin Chim Acta. 2025 Jan 8:568:120130. doi: 10.1016/j.cca.2025.120130. Online ahead of print.

Authors

Takahide Kokumai¹, Shigeru Suzuki², Satoru Takahashi³, Toshika Okumiya⁴, Masafumi Koga⁵

Affiliations

¹ Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Japan. Electronic address: tkokumai5p@asahikawa-med.ac.jp.
² Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Japan. Electronic address: shige5p@asahikawa-med.ac.jp.
³ Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Japan. Electronic address: satoru5p@asahikawa-med.ac.jp.
⁴ Department of Medical Laboratory Science, Kochi Gakuen University, 292-26 Asahitenjincho, Kochi 780-0955, Japan. Electronic address: tokumiya@kochi-gu.ac.jp.
⁵ Department of Internal Medicine, Hakuhokai Central Hospital, 4-23-1 Higahisonodacho, Amagasaki 661-0953, Japan. Electronic address: koga2636@gmail.com.

PMID: 39793848
DOI: 10.1016/j.cca.2025.120130

Abstract

Background: HbA1c levels are affected by both glycemia and erythrocyte lifespan. Erythrocyte creatine (EC) indicates mean erythrocyte age. Although EC levels differ between adolescent males and females, with higher levels in females, the mechanism remains unclear. We examined the EC and HbA1c levels in non-diabetic children.

Methods: This study included 85 children aged 3-18 years (male/female: 44/41) without diabetes or anemia. Data on EC, age, HbA1c, glycated albumin (GA), casual plasma glucose (PG), and complete blood count were measured. We examined correlation among EC, age, and HbA1c levels separately in males and females. Additionally, we compared women with and without menstruation.

Results: Age, EC, HbA1c, GA, and PG levels were comparable between the sexes. HbA1c levels were not correlated with age in either group (males: R = 0.063, p = 0.684; females: R = 0.112, p = 0.486). In males, EC levels were not correlated with age (R = 0.089, p = 0.567), but showed a negative trend with HbA1c (R = 0.281, p = 0.065). In females, EC levels were positively correlated with age (R = 0.557, p < 0.001), but not with HbA1c (R = 0.140, p = 0.383). Females with menstruation had higher EC levels (1.64 ± 0.43 µmol/g Hb) than those without menstruation (1.23 ± 0.23 µmol/g Hb, p = 0.004): however, HbA1c differences were not significant (5.44 ± 0.28 % vs, 5.41 ± 0.22 %, p = 0.771).

Conclusions: No significant correlation was observed between EC and HbA1c levels in non-diabetic and non-anemic children. However, the discrepancy between HbA1c and EC levels in relation to age in females was observed. These findings indicate that in females, but not in males, EC may be falsely elevated irrespective of erythrocyte lifespan after puberty.

Keywords: Erythrocyte creatine; HbA1c; Menstruation.