Dataset Information

Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population.

ABSTRACT: C-peptide measurement may represent a better index of pancreatic ?-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and the development of type 2 diabetes independent of glucose and insulin levels and to examine potential effect-modification by variables related to kidney function. We included 5176 subjects of the Prevention of Renal and Vascular End-Stage Disease study without type 2 diabetes at baseline. C-peptide was measured in plasma with an electrochemiluminescent immunoassay. Cox proportional hazards regression was used to evaluate the association between C-peptide level and type 2 diabetes development. Median C-peptide was 722 (566-935) pmol/L. During a median follow-up of 7.2 (6.0-7.7) years, 289 individuals developed type 2 diabetes. In multivariable-adjusted Cox regression models, we observed a significant positive association of C-peptide with the risk of type 2 diabetes independent of glucose and insulin levels (hazard ratio (HR): 2.35; 95% confidence interval (CI): 1.49-3.70). Moreover, we found significant effect modification by hypertension and albuminuria (p < 0.001 and p = 0.001 for interaction, respectively), with a stronger association in normotensive and normo-albuminuric subjects and absence of an association in subjects with hypertension or albuminuria. In this population-based cohort, elevated C-peptide levels are associated with an increased risk of type 2 diabetes independent of glucose, insulin levels, and clinical risk factors. Elevated C-peptide level was not independently associated with an increased risk of type 2 diabetes in individuals with hypertension or albuminuria.

SUBMITTER: Sokooti S

PROVIDER: S-EPMC7564789 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population.

Sokooti Sara S Kieneker Lyanne M LM Borst Martin H de MH Muller Kobold Anneke A Kootstra-Ros Jenny E JE Gloerich Jolein J van Gool Alain J AJ Heerspink Hiddo J Lambers HJL T Gansevoort Ron R Dullaart Robin P F RPF Bakker Stephan J L SJL

Journal of clinical medicine 20200917 9

C-peptide measurement may represent a better index of pancreatic β-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and the development of type 2 diabetes independent of glucose and insulin levels and to examine potential effect-modification by variables related to kidney function. We included 5176 subjects of the Prevention of Renal ...[more]

PMID: 32957570

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Project description:BackgroundType 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.MethodsWe 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.ResultsWe 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).ConclusionFasting 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.

Project description:ObjectivesThis study aimed to provide an overview of prediction models of undiagnosed type 2 diabetes mellitus (U-T2DM) or the incident T2DM (I-T2DM) using the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) checklist and the prediction model risk of the bias assessment tool (PROBAST).Data sourcesBoth PUBMED and EMBASE databases were searched to guarantee adequate and efficient coverage.Study selectionArticles published between December 2011 and October 2019 were considered.Data extractionFor each article, information on model development requirements, discrimination measures, calibration, overall performance, clinical usefulness, overfitting, and risk of bias (ROB) was reported.ResultsThe median (interquartile range; IQR) number of the 46 study populations for model development was 5711 (1971 - 27426) and 2457 (2060 - 6995) individuals for I-T2DM and U-T2DM, respectively. The most common reported predictors were age and body mass index, and only the Qrisk-2017 study included social factors (e.g., Townsend score). Univariable analysis was reported in 46% of the studies, and the variable selection procedure was not clear in 17.4% of them. Moreover, internal and external validation was reported in 43% the studies, while over 63% of them reported calibration. The median (IQR) of AUC for I-T2DM models was 0.78 (0.74 - 0.82); the corresponding value for studies derived before October 2011 was 0.80 (0.77 - 0.83). The highest discrimination index was reported for Qrisk-2017 with C-statistics of 0.89 for women and 0.87 for men. Low ROB for I-T2DM and U-T2DM was assessed at 18% and 41%, respectively.ConclusionsAmong prediction models, an intermediate to poor quality was reassessed in several aspects of model development and validation. Generally, despite its new risk factors or new methodological aspects, the newly developed model did not increase our capability in screening/predicting T2DM, mainly in the analysis part. It was due to the lack of external validation of the prediction models.

Dataset Information

Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population.

Publications

Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population.

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