High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Abstract

Objective Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes.

Role of Advanced Glycation End Products on Aortic Calcification in Patients with Type 2 Diabetes Mellitus

“…On the other hand, we find an association between circulating AGEs and HbA1c. Similar results have been found in other studies [35] where AGEs levels were higher in patients with poor glycemic control measured by HbA1c [54,[57][58][59]. It is important to consider that the extent and duration of hyperglycemia are predicted by increased levels of HbA1c, which is considered an acceptable marker.…”

Body mass index ≥23 is a risk factor for insulin resistance and diabetes in Japanese people: A brief report

“…The mean GIR during this time was defined as the glucose disposal rate (GDR), which was used as a marker of peripheral insulin sensitivity. The glucose clamp method is a well-established procedure at our hospital [ 11 , 14 ].…”

In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet‐Related Advanced Glycation End Products and Related 1,2‐Dicarbonyls

“…These concentrations are much lower than our maximum concentration tested, i.e., 1 mol/L, which does not exert any cytotoxic effect triggered by these two glycated amino acids. In the case of MG-H1, its concentration according to several studies in serum of nondiabetic patients is at 76.67 ± 35.93 nmol/L [ 50 ] and in plasma at 109.97 ± 46.00 nmol/L [ 51 ]. Moreover, the daily intake of CEL was calculated to be ~0.01 mmol, of CML~0.015 mmol, and MG-H1~0.1 mmol.…”