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Plasma creatine and incident type 2 diabetes in a general population‐based cohort: The PREVEND study
Author(s) -
Post Adrian,
Groothof Dion,
Schutten Joëlle C.,
FloresGuerrero Jose L.,
Swarte J. Casper,
Douwes Rianne M.,
Kema Ido P.,
Boer Rudolf A.,
Garcia Erwin,
Connelly Marge A.,
Wallimann Theo,
Dullaart Robin P. F.,
Franssen Casper F. M.,
Bakker Stephan J. L.
Publication year - 2021
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.14396
Subject(s) - medicine , creatine , endocrinology , type 2 diabetes , diabetes mellitus , population , insulin , insulin resistance , environmental health
Background Type 2 diabetes is associated with both impaired insulin action at target tissues and impaired insulin secretion in pancreatic beta cells. Mitochondrial dysfunction may play a role in both insulin resistance and impaired insulin secretion. Plasma creatine has been proposed as a potential marker for mitochondrial dysfunction. We aimed to investigate the association between plasma creatine and incident type 2 diabetes. Methods We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the general population‐based PREVEND study. The study outcome was incident type 2 diabetes, defined as a fasting plasma glucose ≥7.0 mmol/L (126 mg/dl); a random sample plasma glucose ≥11.1 mmol/L (200 mg/dl); self‐report of a physician diagnosis or the use of glucose‐lowering medications based on a central pharmacy registration. Associations of plasma creatine with type 2 diabetes were quantified using Cox proportional hazards models and were adjusted for potential confounders. Results We included 4735 participants aged 52 ± 11 years, of whom 49% were male. Mean plasma creatine concentrations were 36.7 ± 17.6 µmol/L, with lower concentrations in males than in females (30.4 ± 15.1 µmol/L vs. 42.7 ± 17.7 µmol/L; p for difference <.001). During 7.3 [6.2–7.7] years of follow‐up, 235 (5.4%) participants developed type 2 diabetes. Higher plasma creatine concentrations were associated with an increased risk of incident type 2 diabetes (HR per SD change: 1.27 [95% CI: 1.11–1.44]; p < .001), independent of potential confounders. This association was strongly modified by sex ( p interaction <.001). Higher plasma creatine was associated with an increased risk of incident type 2 diabetes in males (HR: 1.40 [1.17–1.67]; p < .001), but not in females (HR: 1.10 [0.90–1.34]; p = .37). Conclusion Fasting plasma creatine concentrations are lower in males than in females. Higher plasma creatine is associated with an increased risk of type 2 diabetes in males.