Volatile metabolites in sera of normal and diabetic patients

Zlatkis, A.; Poole, Colin F.; Brazeli, Roswitha; Bafus, Donald A.; Spencer, Peter S.

doi:10.1016/s0378-4347(00)81617-5

Cited by 38 publications

(16 citation statements)

References 14 publications

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“…The type and amount of these volatiles were shown to vary with treatment regime. 29,30,33 Further to this point, those with Type 1 diabetes were also found to excrete higher levels of ethanol and propanol than controls; however, controls excreted significantly greater amounts of C 4 and C 5 alcohols. 31 Those with Type 2 diabetes were distinguished from controls by significantly higher levels of propanol in their urine specimens.…”

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confidence: 86%

“…Several investigators applied these techniques to individuals with juvenile and Type 1 diabetes, examining urine (previously reviewed [19][20][21][22][23][24][25][26][27][28][29][30][31], saliva, 32 and plasma 29,33 from individuals with and without high blood glucose levels as well as individuals under different treatment regimes. These studies demonstrated that other volatiles besides acetone are present in breath and urine of patients with diabetes.…”

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confidence: 99%

“…36 Substantial differences have been documented in the urinary and serum volatiles from individuals with diabetes (Type 1), versus normal controls, using GC and GC/MS. [29][30][31]33,39 Compounds that were reported to be characteristic of urine samples from individuals with diabetes under insulin therapy were pyrazines, cyclohexanone, C 2 -C 5 alcohols, isomeric C 8 alcohols, and C 6 and C 7 ketones. The type and amount of these volatiles were shown to vary with treatment regime.…”

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confidence: 99%

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Volatile Metabolic Monitoring of Glycemic Status in Diabetes Using Electronic Olfaction

Dalton

Gelperin²,

Preti³

2004

Diabetes Technology & Therapeutics

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The increased incidence of Type I and Type II diabetes among adults and adolescents is a growing public health concern worldwide. The primary objective of diabetes mellitus management involves keeping glycemia levels within the euglycemic range to prevent a variety of serious health complications. Unfortunately, daily self-monitoring is both a requirement and a problem for many patients with diabetes, particularly children and adolescents. Studies have shown that as many as 43% of adolescents and 30% of children (<14 years old) regularly forget to use glycemic tests and are significantly poorer at recognizing and reporting symptoms and signs of hypoglycemia/hyperglycemia. For this reason, methods for noninvasive, continuous monitoring that can signal glycemic status to a parent, teacher, or other caregiver would improve the care and management of symptoms of diabetes among these individuals. The goal of this review is to describe and evaluate electronic olfaction technology ("electronic nose") for monitoring the presence and levels of volatile chemicals from human body and breath that can be used to evaluate status of diabetes. The review is organized in four sections. The first section reviews the chemistry of the volatile signals that are produced by the body that are indicative of metabolic status. The second section provides an overview of novel sensor technology, e.g., "electronic olfaction," that mimics the biological olfactory system and can be used to monitor and identify complex plumes of volatiles that are signatures of metabolic states. The third section reviews studies that have employed electronic "nose" technology for diagnosis and monitoring of diabetes via urine and breath, and the final section discusses needed future directions for the development of olfactory-based metabolic monitoring, particularly among noncompliant populations.

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confidence: 86%

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confidence: 99%

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confidence: 99%

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Volatile Metabolic Monitoring of Glycemic Status in Diabetes Using Electronic Olfaction

Dalton

Gelperin²,

Preti³

2004

Diabetes Technology & Therapeutics

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“…The low recovery of CdG 1 was due in part to its poor labeling efficiency (22 (4). Crotonaldehyde has been found in the blood of healthy individuals (25). Acrolein can also be formed intracellularly by enzymatic oxidation of polyamines (26).…”

Section: Levels and Stereoselective Formation Of Adg And Cdg Inmentioning

confidence: 99%

Detection of exocyclic 1,N2-propanodeoxyguanosine adducts as common DNA lesions in rodents and humans.

Nath

Chung

1994

Proc. Natl. Acad. Sci. U.S.A.

237

283

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Exocyclic adducts are unique DNA modifications resulting from bindin at two sites of bases that normally are involved in hydrogen-boning for maintaining the doublehelical structure of DNA. These adducts have been shown to be formed in rodents upon exposure to carcinogens. Using a sensitive 32P-postlabeling method combined with high performance liquid chromatography, we obtained evidence that 1,N2-propanodeoxyguanosine adducts of acrolein (AdG) and crotonaldehyde (CdG) are present in the liver DNA of humans and rodents without carcinogen treatment. (22). In this study, we used this method to show that AdG and CdG (Fig. 1) are present in the liver DNA of rodents and humans and that the in vivo formation of these adducts appears to be stereoselective. MATERIALS AND METHODS DNA Isolation and Hydrolysis and Collection of AdductFractions by HPLC. Male A/J mice (25-30 g) and Fischer rats (200-230 g) were purchased from Charles River Breeding Laboratories and housed in polycarbonate cages (250C ± 2TC, 50 ± 10% relative humidity, and 12-hr light/dark cycle). These animals were fed the modified AIN-76A diet and tap water ad libitum. After 3 weeks of acclimatization, all animals were sacrificed. Livers were quickly removed, minced, and frozen at -800C until DNA isolation. DNA was isolated by a modified Marmur's procedure (23). DNA samples were stored at -800C until analysis.DNA (105-300 pg) was obtained from livers ofeach offour mice and four rats and from each of five humans (two males of ages 37 and 94 years; three females of ages ranging from 50 to 60 years). Human liver DNA was isolated from autopsy samples and was provided by Regina Santella (Columbia University). The DNA was enzymatically hydrolyzed to 3'-monophosphates (22). The enzyme digest was filtered through a 0.2-gm Acrodisc Mini Spike syringe filter (Gelman) and was analyzed by HPLC system 1. Fractions corresponding to AdG 3'-monophosphate and CdG 3'-monophosphate were collected according to the retention times of the synthetic standards (22). To ensure that the assay was free of contamination, blank samples were obtained after injecting 300 p4 of water prior to the collection of fractions of DNA hydrolysates from each species. The fractions from the Abbreviations: enals, a,jf-unsaturated aldehydes; AdG, acroleinderived 1,N2-propanodeoxyguanosine; CdG, crotonaldehydederived 1,N2-propanodeoxyguanosine.*To whom reprint requests should be addressed. 7491The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…This disrupts longitudinal axonal transport and eventually results in distal axonal degeneration of elongate large-diameter myelinated nerve fibers. [11][12][13][14] Since the serum of individuals with and without DM has been documented to contain 2-hexanone and 3-heptanone, 15 both of which can undergo w-1 oxidation to form the neurotoxic γ-diketones 2,5-HD and 3,6-heptanedione, respectively, that form amine pyrroles, [15][16][17] we tested the novel hypothesis that elevated concentrations of γ-diketone pyrroles are present in diabetic urine.…”

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confidence: 99%

Diabetes mellitus is associated with elevated urinary pyrrole markers of γ-diketones known to cause axonal neuropathy

Chen

Liu

Wang

et al. 2020

BMJ Open Diab Res Care

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IntroductionProgressive distal symmetrical axonal neuropathy, a complication of diabetes mellitus (DM), has an unknown cause. Normal physiological metabolism and diabetic dysmetabolism are associated with the generation of γ-diketones. γ-Diketones form pyrroles with protein amines, notably with axonal proteins required for the maintenance of nerve fiber integrity, especially elongate, large-diameter peripheral nerve fibers innervating the extremities. We tested the hypothesis that neuropathy-associated γ-diketone pyrroles are elevated in DM.Research design and methodsWe measured the urinary concentration of γ-diketone pyrroles in age-matched and gender-matched elderly (60–84 years) persons with (n=267) or without (n=267) indicators of DM based in a community population (9411 community older adults aged ≥60 years) in Shenzhen city, Guangdong, China. We used statistical methods, including a generalized linear model, multivariate logistic regression analysis and restricted cubic splines, to assess linear and nonlinear relationships between urinary γ-diketone pyrroles and indicators of DM.ResultsCompared with healthy controls, those with DM had significantly higher levels of fasting blood glucose, glycated hemoglobin A1c, urinary ketone bodies and urinary γ-diketone pyrroles. The median concentration of urinary γ-diketone pyrrole adducts was significantly higher (p<0.0001) in individuals with DM (7.5 (5.4) μM) compared with healthy controls (5.9 (4.3) μM). Both linear and non-linear relations were found between urinary γ-diketone pyrroles and indicators of DM.ConclusionsDiabetic dysmetabolism includes increased generation and excretion of neuropathy-associated γ-diketone pyrroles. These findings form the foundation for studies to test whether γ-diketone pyrrole concentration correlates with quantitative sensory (vibration and temperature) and electrodiagnostic testing.

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Volatile metabolites in sera of normal and diabetic patients

Cited by 38 publications

References 14 publications

Volatile Metabolic Monitoring of Glycemic Status in Diabetes Using Electronic Olfaction

Volatile Metabolic Monitoring of Glycemic Status in Diabetes Using Electronic Olfaction

Detection of exocyclic 1,N2-propanodeoxyguanosine adducts as common DNA lesions in rodents and humans.

Diabetes mellitus is associated with elevated urinary pyrrole markers of γ-diketones known to cause axonal neuropathy

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