Related Experiment Video

Updated: Jun 12, 2025

Glycemic Impact on Knee Osteoarthritis Symptoms on Physical, Radiographic, and Inflammatory Markers among Individuals Aged 50 and Over with Diabetes

Glycemic Impact on Knee Osteoarthritis Symptoms on Physical, Radiographic, and Inflammatory Markers among Individuals Aged 50 and Over with Diabetes

Published on: March 7, 2025

Methylglyoxal Mediates the Association Between 2-Hour Plasma Glucose and HbA1c With Inflammation: The Maastricht

Dijia Sun^1,2, Marleen M J van Greevenbroek^1,2, Jean L J M Scheijen^1,2

¹Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.

The Journal of Clinical Endocrinology and Metabolism

|September 24, 2024

Abstract

Context:

Glucose excursions in persons with diabetes may drive chronic inflammation. Methylglyoxal (MGO) is formed from glucose, is elevated in persons with diabetes, and is a potent glycating agent linked with inflammation.

Objective:

We investigated whether glucose excursions are associated with low-grade inflammation and whether MGO mediates this association.

Methods:

We used data from The Maastricht Study, an extensive phenotyping study into the etiology of type 2 diabetes and its complications. Data of 3017 participants, who underwent an oral glucose tolerance test and where data on MGO levels and inflammation were available, were used. Linear regression analyses, adjusted for potential confounders, evaluated associations between fasting plasma glucose (FPG), 2-hour plasma glucose (2h-PG) and HbA1c, and low-grade inflammation (stdβ, [95% CI]) were calculated from plasma concentrations of C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, tumor necrosis factor, and soluble intercellular adhesion molecule-1. Mediation analyses investigated whether MGO mediated these associations.

Results:

2h-PG (0.172, [0.110; 0.234]) and HbA1c (0.148, [0.101; 0.196]), but not FPG (0.049, [-0.002; 0.100]), were associated with low-grade inflammation. 2h-PG and HbA1c were also associated with 2h-MGO (0.471, [0.407; 0.534], and 0.244, [0.195; 0.294], respectively). Furthermore, 2h-MGO was independently and positively associated with low-grade inflammation (0.078, [0.037; 0.120]). 2h-MGO mediated 23% of the association between 2h-PG and inflammation, and 16% of the association between HbA1c and inflammation.

Conclusion:

MGO mediates the association between postload glucose excursions and HbA1c with inflammation, providing evidence for a role of postprandial MGO formation to hyperglycemia-induced low-grade inflammation.

Keywords:

cardiovascular complications diabetes inflammation methylglyoxal

More Related Videos

Analyzing the Permeability of the Blood-Brain Barrier by Microbial Traversal through Microvascular Endothelial Cells

Analyzing the Permeability of the Blood-Brain Barrier by Microbial Traversal through Microvascular Endothelial Cells

Published on: February 14, 2020

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT

Published on: January 7, 2018

Related Concept Videos

Diabetes Mellitus: Type 2 and Gestational

Diabetes Mellitus: Type 2 and Gestational

Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...

Hormones Regulating Blood Glucose

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...

Hypoglycemia and Glucagon

Hypoglycemia and Glucagon

Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...

Diabetes: Symptoms, Diagnosis, and Complications

Diabetes: Symptoms, Diagnosis, and Complications

For most patients, experiencing several weeks of polyuria, polydipsia, fatigue, and significant weight loss may indicate the presence of diabetes. Furthermore, adults displaying the phenotypic appearance of type 2 diabetes (particularly those who are obese and not initially insulin-requiring), may have islet cell autoantibodies, suggesting autoimmune-mediated β cell destruction and a diagnosis of latent autoimmune diabetes of adults (LADA). The categorization of glucose homeostasis is...

Pathophysiology of Diabetes

Pathophysiology of Diabetes

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...

Overview of Carbohydrate Metabolism

Overview of Carbohydrate Metabolism

Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to living cells. The most important carbohydrate is glucose, which can be broken down via glycolysis to enter into the Krebs cycle and eventually lead to the production of ATP through oxidative phosphorylation.
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...

Articles linked to this work by shared authors, journal, and citation graph.

Metabolic benefits of ketohexokinase inhibition in individuals with MASLD: a randomized placebo-controlled crossover trial.

Nature metabolism·2026

Circulating levels of glucoselysine, a fructose-specific glycation product, are modulated by dietary fructose; post-hoc analysis of a case-control study and a randomized controlled trial.

The American journal of clinical nutrition·2026

Changes in plasma levels of a selected panel of miRNAs do not explain the shift from cholesterol-synthesizer to cholesterol-absorber phenotype in men with abdominal obesity after diet-induced weight loss.

International journal of obesity (2005)·2026

Longitudinal Profiling Reveals Divergent Kidney and Brain Immune Responses during Metabolic Syndrome.

Aging and disease·2026

Endogenous fructose production in patients and mice with aldolase B deficiency.

Molecular genetics and metabolism·2026

Plasma-based low-grade inflammation and endothelial dysfunction explain a small but significant proportion of the association between the n-3 polyunsaturated fatty acids and cardiovascular diseases: The Maastricht Study.

Journal of clinical lipidology·2026

See all related articles