Glyoxylate, a New Marker Metabolite of Type 2 Diabetes

Abstract

Type 2 diabetes (T2D) is characterized by a variety of metabolic impairments that are closely linked to nonenzymatic glycation reactions of proteins and peptides resulting in advanced glycation end-products (AGEs). Reactive aldehydes derived from sugars play an important role in the generation of AGEs. Using metabolite profiling to characterize human plasma from diabetic versus nondiabetic subjects we observed in a recent study that the reactive aldehyde glyoxylate was increased before high levels of plasma glucose, typical for a diabetic condition, could be measured. Following this observation, we explored the relevance of increased glyoxylate in diabetic subjects and in diabetic C57BLKS/J-Leprdb/db−/− mice in the pathophysiology of diabetes. A retrospective study using samples of long-term blood donors revealed that glyoxylate levels unlike glucose levels became significantly elevated up to 3 years prior to diabetes diagnosis (difference to control P = 0.034). Elevated glyoxylate levels impact on newly identified mechanisms linking hyperglycemia and AGE production with diabetes-associated complications such as diabetic nephropathy. Glyoxylate in its metabolic network may serve as an early marker in diabetes diagnosis with predictive qualities for associated complications and as potential to guide the development of new antidiabetic therapies.

Metabolite profiling in plasma and tissues of ob/ob and db/db mice identifies novel markers of obesity and type 2 diabetes

“…Twenty-four metabolites changed specifically in the plasma of db/db mice (Table 2), of which 12 remained significant after p value adjustment. Besides increases in glucose, elevated levels of glyoxylate were found, which we recently described as a diabetes marker [10]. In addition, corticosterone and 18-hydroxy-11-deoxycorticosterone concentrations were markedly elevated.…”

“…ESM Table 3 displays the overall significance of the clusters reached for the two knockout models as compared with wild-type mice. Five metabolite clusters displayed high significance for both knockout models (clusters 4,8,10,13,15), consisting of phospholipids, triacylglycerols, AAA and BCAA, as well as glycine, histidine and trans-4-hydroxyproline. Interestingly, four clusters (clusters 1, 5, 9, 11)-mainly consisting of amino acids, hexoses and catabolites-showed overall significant changes only between db/db and C57BLKS/J wild-type mice.…”

Hepatic Dysfunction Caused by Consumption of a High-Fat Diet

“…SRC-1), depletion of which can result in increased glucose uptake, enhanced insulin sensitivity, and resistance to age-associated obesity and glucose intolerance (Wang et al, 2012). A literature review revealed additional Steiner nodes with known relevance to disease, including the metabolite glyoxylic acid, which has been characterized as a marker metabolite for type 2 diabetes (Nikiforova et al, 2014). Thus, our model incorporates many predicted nodes with known relevance to these conditions, though many are not well-established actors in these contexts.…”

Complete metabolome and lipidome analysis reveals novel biomarkers in the human diabetic corneal stroma

“…Studies have identified glyoxylate as a biomarker for early detection of Type 2 diabetes (Nikiforova et al, 2014). In our study, we measured little variation between glyoxylate levels in the diabetic cornea compared to healthy controls (Figure 3).…”