Carboxymethyl lysine, an advanced glycation end product, and incident diabetes: a case-cohort analysis of the ARIC Study.
Pubmed ID: 26359784
Pubmed Central ID: PMC4929039
Journal: Diabetic medicine : a journal of the British Diabetic Association
Publication Date: Oct. 1, 2016
MeSH Terms: Humans, Male, Female, Case-Control Studies, Risk Factors, Cohort Studies, Middle Aged, Incidence, Diabetic Angiopathies, Diabetes Mellitus, Atherosclerosis, Glycation End Products, Advanced, Lysine
Grants: HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01 DK056918, HHSN268201100009I, HHSN268201100005G, HHSN268201100008I, HHSN268201100011I, HHSN268201100005I, HHSN268201100007I, N01HC55018
Authors: Pankow JS, Couper DJ, Chambless LE, Heiss G, Luft VC, Duncan BB, Schmidt MI, Hoogeveen RC
Cite As: Luft VC, Duncan BB, Schmidt MI, Chambless LE, Pankow JS, Hoogeveen RC, Couper DJ, Heiss G. Carboxymethyl lysine, an advanced glycation end product, and incident diabetes: a case-cohort analysis of the ARIC Study. Diabet Med 2016 Oct;33(10):1392-8. Epub 2015 Oct 6.
Studies:
Abstract
AIMS: To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end product, predict the development of diabetes in middle-age adults. METHODS: Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design. RESULTS: In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually < 0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, BMI, waist-to-hip ratio, non-esterified fatty acids, oxidized LDL-cholesterol, GFR, smoking, an inflammation score, adiponectin, leptin, insulin and glucose levels, was associated with an increased risk of diabetes [Hazard ratio (HR) = 1.35; 95% confidence interval (CI) 1.09-1.67, for each 100 ng/ml CML increment]. Baseline glucose level and race each modified the association (P < 0.05 for interaction), which was present only among those with impaired fasting glucose (≥ 5.6 mmol/l, HR = 1.61, 95% CI 1.26-2.05) and among white participants (HR = 1.50, 95% CI 1.13-1.99). CONCLUSIONS: Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in white participants. These prospective findings suggest that advanced glycation end products might play a role in the development of diabetes.