Differential metabolomic signatures of declining renal function in Types 1 and 2 diabetes

Abstract

Background Chronic kidney disease (CKD) shows different clinical features in Types1 (T1D) and 2 diabetes (T2D). Metabolomics have recently provided useful contribution to the identification of biomarkers of CKD progression in either form of the disease. However, no studies have so far compared plasma metabolomics between T1D and T2D in order to identify differential signatures of progression of estimated glomerular filtration rate (eGFR) decline. Methods We used two large cohorts of T1D (from Finland) and T2D (from Italy) patients followed up to 7 and 3 years, respectively. In both groups, progression was defined as the top quartile of yearly decline in eGFR. Pooled data from the two groups were analysed by univariate and bivariate random forest (RF), and confirmed by bivariate partial least squares (PLS) analysis, the response variables being type of diabetes and eGFR progression. Results In progressors, yearly eGFR loss was significantly larger in T2D [−5.3 (3.0), median (interquartile range)mL/min/1.73 m2/year] than T1D [−3.7 (3.1) mL/min/1.73 m2/year ; P = 0.018]. Out of several hundreds, bivariate RF extracted 22 metabolites associated with diabetes type (all higher in T1D than T2D except for 5-methylthioadenosine, pyruvate and β-hydroxypyruvate) and 13 molecules associated with eGFR progression (all higher in progressors than non-progressors except for sphyngomyelin). Three of the selected metabolites (histidylphenylalanine, leucylphenylalanine, tryptophylasparagine) showed a significant interaction between disease type and progression. Only eight metabolites were common to both bivariate RF and PLS. Conclusions Identification of metabolomic signatures of CKD progression is partially dependent on the statistical model. Dual analysis identified molecules specifically associated with progressive renal impairment in both T1D and T2D.

Circulating short and medium chain fatty acids are associated with normoalbuminuria in type 1 diabetes of long duration

“…Similar risk patterns for progressive DKD regarding uremic solutes were also reported in several studies evaluating eGFR-based outcomes 10,11,13,23,58 . In addition, lysolipids, dipeptides and oxidized cholesterol derivatives displayed risk patterns in our study and several others 23,[59][60][61] . Some efforts have also been undertaken to examine albuminuria-based outcomes 23,[62][63][64] .…”

Precise Detection of Cataracts with Specific High‐Risk Factors by Layered Binary Co‐Ionizers Assisted Aqueous Humor Metabolic Analysis

“…Meanwhile, the approximate down‐regulation of proly‐Lysine in CDM is also observed, indirectly echoing with the consistency of change trend of glucose concentration in CDM and CHM (Figure 6d ) and manifesting the menace of diabetes toward cataracts again. In addition, reports have pointed out that 3‐hydroxypyruvic acid ( m / z 104.0110, [M + H] + ) plays a crucial role in destabilizing hypoxia inducible factor and inducing the irreversible injury of the retina, [ 34 ] which is another representative one associated with high glucose. [ 35 ] As displayed in Figure 3 , 6 , 3‐hydroxypyruvic acid uniformly presents up‐regulation in CDM and CHM compared to ARC, and more up‐regulation in CHM.…”

LC–MS metabolomics reveal skin metabolic signature of psoriasis vulgaris

“…Therefore, l‐gamma‐glutamyl‐l‐leucine was thought to trigger psoriasis by impairing antioxidant system. The another amino acid metabolite, histidylphenylalanine, is a competitive inhibitor of histidine decarboxylase, which indirectly affects the formation of histamine 13 . Histamine may induce inflammatory and pruritus via a multitude of mechanisms in psoriasis, such as promoting an accumulation of immune cells migrating into the dermal infiltrate, inhibiting epidermal differentiation and enhancing its concentrations in psoriatic skin 14 .…”

“…The another amino acid metabolite, histidylphenylalanine, is a competitive inhibitor of histidine decarboxylase, which indirectly affects the formation of histamine. 13 Histamine may induce inflammatory and pruritus via a multitude of mechanisms in psoriasis, such as promoting an accumulation of immune cells migrating into the dermal infiltrate, inhibiting epidermal differentiation and enhancing its concentrations in psoriatic skin. 14 In the present study, histidylphenylalanine levels were elevated in psoriatic lesions, but it has not been reported to be involved in pathogenetic mechanisms of psoriasis, and therefore remains to be further investigated.…”