Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin

Krebs, Andreas; Doerfer, Jürgen; Grünert, Sarah C.; Wöhrl, Jan; Stier, Bernhard; Schmidt‐Trucksäss, Arno; Lichte, Kai; Winkler, Karl; Grulich‐Henn, Jürgen; Holder, Martin; Schwab, Karl Otfried

doi:10.1515/jpem-2014-0083

Cited by 11 publications

(11 citation statements)

References 24 publications

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“…The ADMA and hArg concentrations reported by this group disagree with our observations from the present study with regard to ADMA and hArg and with regard to ADMA in previous studies. Thus, the average ADMA plasma concentration of 1.06 µM in healthy controls (Krebs et al 2015) is almost two times higher than that measured in the HC group of the present study and in healthy children and adolescents of a previous study (Lücke et al 2007). Furthermore, both the physiological variability and the extent of effects of disease or pharmacological treatment on circulating ADMA (Horowitz and Heresztyn 2007;Tsikas 2008) and hArg Pilz et al 2015) concentrations are very low.…”

Section: Amino Acids Of the L-arg/no Pathwaycontrasting

confidence: 62%

“…ADMA is significantly elevated in adults with T1DM with or without diabetic nephropathy (Altinova et al 2007;Cighetti et al 2009;Tarnow et al 2004;Vallance et al 1992 Krebs et al 2015). In the present study, we investigated the status of the Arg/ NO pathway in children and adolescents with T1DM in comparison to non-diabetic HC.…”

Section: Discussionmentioning

confidence: 75%

“…In a recently reported study on 28 children with T1DM (median age, 14.5 years) and 41 healthy controls (median age, 14 years), median circulating hArg (0.9 vs 1.42 µM, difference, 37 %) and ADMA (0.4 vs 1.06 µM; difference, 62 %) were found to be considerably lower (P < 0.001 each) in T1DM compared to healthy non-diabetic children (Krebs et al 2015). To our knowledge, this is the first study to report on hArg concentrations in children with T1DM.…”

Section: Amino Acids Of the L-arg/no Pathwaymentioning

confidence: 83%

“…Several groups have measured ADMA, hArg and HbA 1c and tested for potential correlation between circulating ADMA or hArg and HbA 1c in children suffering from T1DM (Heilman et al 2009;Głowińska-Olszewska et al 2010;Huemer et al 2011;Marcovecchio et al 2011;Önder et al 2014;Krebs et al 2015) (Table 7). In a recently reported study on 28 children with T1DM (median age, 14.5 years) and 41 healthy controls (median age, 14 years), median circulating hArg (0.9 vs 1.42 µM, difference, 37 %) and ADMA (0.4 vs 1.06 µM; difference, 62 %) were found to be considerably lower (P < 0.001 each) in T1DM compared to healthy non-diabetic children (Krebs et al 2015).…”

Section: Amino Acids Of the L-arg/no Pathwaymentioning

confidence: 99%

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The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus

et al. 2015

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High circulating levels of asymmetric dimethylarginine (ADMA) and low circulating levels of homoarginine (hArg) are known cardiovascular risk factors in adults. While in adults with type 1 diabetes mellitus (T1DM) circulating ADMA is significantly elevated, in children and adolescents the reported ADMA data are contradictory. In 102 children with T1DM and 95 healthy controls (HC) serving as controls, we investigated the L-arginine (Arg)/nitric oxide (NO) pathway. Children with T1DM were divided into two groups, i.e., in children with newly diagnosed diabetes mellitus [T1DM-ND; n = 10; age, 8.8 (4.4-11.2) years; HbA1c, 13 (8.9-13.9) %] and in those with long-term treatment [T1DM-T; n = 92; age, 12.5 (10.5-15.4) years; HbA1c, 8.0 (7.2-8.6) %]. The age of the HC was 11.3 (8-13.3) years. Amino acids and NO metabolites of the Arg/NO pathway, creatinine and the oxidative stress biomarker malondialdehyde (MDA) were measured by GC-MS or GC-MS/MS. Plasma hArg, ADMA and the hArg/ADMA molar ratio did not differ between the T1DM and HC groups. There was a significant difference between T1DM-T and HC with regard to plasma nitrite [0.53 (0.48-0.61) vs 2.05 (0.86-2.36) µM, P < 0.0001] as well as to urinary nitrite [0.09 (0.06-0.17) vs 0.22 (0.13-0.37) μmol/mmol creatinine, P < 0.0001]. Plasma, but not urinary nitrite, differed between T1DM-ND and HC [0.55 (0.50-0.66) vs 2.05 (0.86-2.36) µM, P < 0.0001]. Plasma MDA did not differ between the groups. The urinary nitrate-to-nitrite molar ratio (UNOXR), a measure of nitrite-dependent renal carbonic anhydrase (CA) activity, was higher in T1DM-T [1173 (738-1481), P < 0.0001] and T1DM-ND [1341 (1117-1615), P = 0.0007] compared to HC [540 (324-962)], but did not differ between T1DM-T and T1DM-ND (P = 0.272). The lower nitrite excretion in the children with T1DM may indicate enhanced renal CA-dependent nitrite reabsorption compared with healthy children. Yet, lower plasma nitrite concentration in the T1DM patients may have also contributed to the higher UNOXR. Patients' age correlated positively with plasma hArg and hArg/ADMA and urinary DMA/ADMA. Plasma ADMA and urinary ADMA, DMA, nitrite and nitrate correlated negatively with age of the T1DM-T children. Significant correlations were found between plasma hArg and plasma Arg (r = 0.468, P < 0.0001), and urinary DMA (r = -0.426, P = 0.0001), ADMA (r = -0.266, P = 0.021) and nitrate (r = -0.234, P = 0.043). Plasma hArg correlated positively with age at diagnosis (r = +0.337, P = 0.002). ADMA, but not hArg, correlated with HbA1c in T1DM-T (r = -0.418, P < 0.0001) and T1DM-ND (r = +0.879, P = 0.0016). The greatest differences between T1DM-T and T1DM-ND were observed for urinary ADMA, DMA/ADMA ratio, nitrite and nitrate. The Arg/NO pathway is altered in T1DM in childhood and adolescence, yet the role and the importance of hArg and ADMA in T1DM remain to be elucidated. In young T1DM patients, oxidative stress (lipid peroxidation) is not elevated.

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Section: Amino Acids Of the L-arg/no Pathwaycontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 75%

Section: Amino Acids Of the L-arg/no Pathwaymentioning

confidence: 83%

Section: Amino Acids Of the L-arg/no Pathwaymentioning

confidence: 99%

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The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus

et al. 2015

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“…reduced in adults with DM2 [9] and DM1 [10,11], as well as in youths with DM1 [12][13][14] when compared with healthy control subjects, and negatively related to glycemic control [9]. This suggests a complex and variable effect of chronic hyperglycemia on plasma levels of ADMA.…”

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confidence: 99%

Asymmetric dimethylarginine is negatively correlated with hyperglycemia in children

et al. 2015

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Homoarginine in the renal and cardiovascular systems

et al. 2015

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Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid which differs from arginine by an additional methylene (CH2) group in the backbone. In this brief narrative review, we summarize the current literature on hArg in the renal and cardiovascular systems. Epidemiological studies have identified low hArg levels as an independent risk marker for cardiovascular, cerebrovascular, and renal diseases as well as for mortality. The relatively low correlation of hArg with established cardiovascular risk factors underlines its great potential as an emerging biomarker to improve risk prediction because plasma hArg concentrations might reflect previously unrecognized pathophysiological processes. hArg may be involved in the pathogenesis of various diseases due to its effects on nitric oxide (NO) and energy metabolism. In view of its structural similarities with arginine, it has been proposed that hArg impacts on arginine metabolism and subsequently also on NO synthesis. The key enzyme for hArg synthesis, arginine:glycine amidinotransferase (AGAT), is involved in the synthesis of energy metabolites including guanidinoacetate, the precursor of creatine. Therefore, the involvement of hArg in energy metabolism could partially explain the close association between hArg and cardiovascular diseases such as heart failure. Whether hArg supplementation or modification of key enzymes of hArg metabolism such as AGAT activity is effective for the treatment of chronic diseases remains to be elucidated.

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Decreased levels of homoarginine and asymmetric dimethylarginine in children with type 1 diabetes: associations with cardiovascular risk factors but no effect by atorvastin

Abstract: Homoarginine and ADMA levels are decreased and associated with cardiovascular risk factors in children with T1D without being affected by atorvastatin.

Cited by 11 publications

References 24 publications

The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus

The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus

Asymmetric dimethylarginine is negatively correlated with hyperglycemia in children

Homoarginine in the renal and cardiovascular systems

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