Serum levels of advanced glycation end products (AGEs) are independent correlates of insulin resistance in nondiabetic subjects.
ABSTRACT Advanced glycation end products (AGEs) evoke oxidative stress generation and inflammatory reactions, thus being involved in vascular complications in diabetes. Since oxidative stress and inflammation impair insulin actions as well, it is conceivable that AGEs may play some role in insulin resistance. However, there is no clinical study to examine the relationship between serum levels of AGEs and insulin resistance. This study investigated whether serum AGE levels were independent correlates of insulin resistance in humans.
Three hundred twenty-two nondiabetic Japanese subjects (216 male and 106 female; mean age 61.5 ± 9.1 years) underwent a complete history and physical examination, determinations of blood chemistries, anthropometric and metabolic variables, including AGEs. Serum AGE levels were examined with an enzyme-linked immunosorbent assay.
Mean serum AGE levels were 8.96 ± 2.57 U/mL. In univariate analysis, waist circumference, diastolic blood pressure (BP), mean BP, AGEs, low-density lipoprotein (LDL) cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol (inversely), hemoglobin A1c (GHb), creatinine clearance, uric acid, and high sensitivity C-reactive protein were significantly associated with insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) index. After performing multiple regression analysis, waist circumference (P < 0.001), GHb (P < 0.001), triglycerides (P < 0.001), and AGEs (P < 0.01) still remained significant independently. When age-adjusted HOMA-IR levels stratified by AGE tertiles were compared using ANCOVA, a significant trend was demonstrated in both males and females.
The present study demonstrated for the first time that serum AGE levels were one of the independent correlates of HOMA-IR index, thus suggesting that AGEs may play some pathological role in insulin resistance in humans.
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ABSTRACT: OBJECTIVE: Although many studies have reported that elevated serum triglycerides to high-density lipoprotein cholesterol (TG-HDL) ratios constitute a risk for insulin resistance and increased arterial stiffness, no study has clarified as yet the association, in terms of the TG-HDL ratio, between diabetes and increased arterial stiffness evaluated by means of carotid intima-media thickness (CIMT) and cardio-ankle vascular index (CAVI). To investigate this association, we conducted a cross-sectional study of 1344 Japanese men aged 36-79 years undergoing a general health check. METHODS: We investigated the associations between atherosclerosis/arterial stiffness, evaluated by means of CIMT and CAVI, and diabetes for all subjects, who were divided into tertiles according to TG-HDL levels. Diabetes was defined as HbA1c (NGSP) ≥6.5%, and/or initiation of glucose-lowering medication or insulin therapy. RESULTS: Of the 130 diabetes patients identified in the cohort, 56 patients had high TG-HDL (high TG-HDL diabetes) and 43 had low TG-HDL (low TG-HDL diabetes). We found that only diabetic patients with high TG-HDL were at a significant risk for atherosclerosis (diagnosed as CIMT ≥ 1.1 mm) and increased arterial stiffness (diagnosed as CAVI ≥ 8.0). The multivariable-adjusted odds ratios and 95% confidence intervals of atherosclerosis and increased arterial stiffness for diabetes were 2.67 (95%CI: 1.35-5.28) and 2.36 (95%CI: 1.01-5.50), for total TG-HDL diabetes 2.57 (95%CI: 1.32-5.02) and 3.56 (95%CI: 1.50-8.46) for high TG-HDL diabetes, and 1.17 (95%CI: 0.52-2.63) and 0.80 (95%CI: 0.33-1.90) for low TG-HDL diabetes, respectively. CONCLUSION: Diabetes, especially high TG-HDL diabetes, constitutes a significant risk for increased arterial stiffness and atherosclerosis.Atherosclerosis 04/2013; · 3.71 Impact Factor
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ABSTRACT: Advanced glycation endproducts (AGEs) form by Maillard-reactions after initial binding of aldehydes with amines or amides in heated foods or in living organisms. The mechanisms of formation may include ionic as well as oxidative and radical pathways. The reactions may proceed within proteins to form high-molecular weight (HMW) AGEs or among small molecules to form low-molecular weight (LMW) AGEs. All free amino acids form AGEs, but lysine or arginine side chains dominate AGE formation within proteins. The analysis of AGEs in foods and body fluids is most often performed by ELISA or LC-MS; however, none of the methodologies cover all HMW and LMW AGEs. Most research is, therefore, carried out using 'representative' AGE compounds, most often Nε-carboxymethyl-lysine (CML). Only LMW AGEs, including peptide-bound forms, and carbonyls may be absorbed from the gut and contribute to the body burden of AGEs. Some AGEs interact with specific pro- or anti-inflammatory receptors. Most studies on the biological effects of AGEs have been carried out by administering heated foods. The pro-inflammatory and deteriorating biological effects of AGEs in these studies, therefore, need further confirmation. The current review points out several research needs in order to address important questions on AGEs in foods and health.Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 07/2013; · 2.99 Impact Factor
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ABSTRACT: To assess the association between arterial stiffness and mild and moderate chronic kidney disease (CKD), independent of other cardiometabolic factors in an elderly population. Cross-sectional study. Health examination data from National Cheng Kung University Hospital from 2006 to 2009. Eligible subjects aged 60 and older (N = 1,251). An average bilateral brachial-ankle pulse wave velocity (baPWV) of 1,400 cm/s or greater was defined as high baPWV. Based on the 2003 Clinical Practice Guidelines for Chronic Kidney Disease from the National Kidney Foundation, mild and moderate CKD were defined as CKD Stages 1 and 2 and Stages 3 to 5, respectively. Participants with a baPWV of 1,400 cm/s or greater (n = 1,028) had lower estimated glomerular filtration rates (eGFRs) but higher serum creatinine levels and greater prevalences of mild and moderate CKD, diabetes mellitus, prediabetes mellitus, hypertension, and prehypertension than those with baPWV less than 1,400 cm/s (n = 223). In the multivariate analysis, mild (odds ratio (OR) = 2.58, 95% confidence interval (CI) = 1.02-6.54) and moderate (OR = 3.75, 95% CI = 1.02-13.81) CKD were positively associated with greater baPWV (≥1,400 cm/s). Age, prediabetes mellitus, diabetes mellitus, prehypertension, and hypertension were also independently associated with greater baPWV. In the multiple linear analysis, moderate (β = 120.45, P < .001) and mild CKD (β = 69.90, P = .01) were positively associated with baPWV. There was also an independently inverse correlation between eGFR and baPWV (β = -0.69, P = .04). Mild and moderate CKD increased the risk of greater arterial stiffness in elderly adults. Age, prediabetes mellitus, diabetes mellitus, prehypertension, and hypertension were also important correlates of increased arterial stiffness.Journal of the American Geriatrics Society 09/2013; · 3.98 Impact Factor