Diabetes Biomarkers Research Articles

Diabetic retinopathy prevention and treatment options

The objective of this review article was to mention the prevalence and risk factors for diabetic retinopathy to occur. Also, mention and compare the best ways to prevent this complication. Adding also a comparison of the best currently available treatments for diabetic retinopathy. Diabetic retinopathy is the first cause of visual impairment in working-age adults worldwide. Duration of diabetes is a major risk factor associated with the development of diabetic retinopathy. Due to the large number of patients with type 2 diabetes, this group comprises a larger proportion of the disease burden in patients with visual impairment from diabetic retinopathy compared to patients with type 1 diabetes. Diabetic retinopathy is the most common cause of visual impairment and blindness in patients aged 20-74 years. Approximately 80% of the patients with type 1 diabetes will develop retinopathy after 15 years after the onset of the pathology. In the case of type 2 diabetes will develop retinopathy after 30 years of history with the disease. Some important factor that can accelerate the process is the use or not of insulin for treatment. The most important for the treatment of diabetic retinopathy is the prevention of the diabetes in healthy people that have the risk factor to develop this pathology. The best options of treatment continued to be the combination of anti-VEFG/panphotocoagulation depending the stage of the complication. Improvement of the early detection of this type of microvascular complication for give them an early treatment and improve the evolution in positive way. We believed that is need to investigate more techniques for early detections of microvascular complications of diabetes mellitus, like imagen or biomarkers.

Isolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy

BackgroundMorus alba Linn, referred to as white mulberry, is a potential traditional medicine for diabetes and neuroprotection. AimIsolation, characterization, development and evaluation of phytoconstituent based formulation for diabetic neuropathy. Material and methodsThe stem Bark of M. alba was peeled and subjected to extraction. A phytoconstituent was then isolated by column chromatography and characterized using Mass spectroscopy, FTIR, and NMR. The isolated phytoconstituent was used to formulate a nanoemulsion. Nanoemulsion was also characterized for viscosity, surface tension, refractive index, pH, and particle size. Selected nanoemulsion formulations were then tested for acute oral toxicity and diabetic neuropathy, including behavioral, hematological, histopathological, and biomarker examinations. ResultsThe spectral analysis affirmed that the isolated compound was found to be chrysin. A nanoemulsion formulation was made using the chrysin and was characterized and found to be stable during the stability testing and fulfilled all other testing parameters. Then acute oral toxicity study of the formulations was found to be safe. Formulations were found to possess significant results against diabetic neuropathy in rats. Biomarkers were analyzed for their mechanistic involvement in reducing neuropathy in rats, and it was found that the oxidative pathway was considerably restored, suggesting that chrysin causes these effects via this pathway. ConclusionsResults suggests that isolated phytoconstituent (chrysin) from the bark of Morus alba derived nanoemulsion has protective and beneficial effects by diminishing the oxidative damage against alloxan-induced diabetic neuropathy in rats.

ZIF-8/MWCNT-nanocomposite based-resistive sensor for highly selective detection of acetone in parts-per-billion: Potential noninvasive diagnosis of diabetes

Zeolitic imidazolate framework-8 (ZIF-8) is a promising metal-organic framework for gas sensing applications in humid conditions due to its inherent hydrophobicity. However, its low sorption capacity for alcohols and acetone at room temperature and atmospheric pressure limits its applications. To overcome this, a novel composite of ZIF-8 and bare multiwall-carbon-nanotubes (MWCNTs) was developed, significantly enhancing its sorption capacity for alcohols and acetone. A ZIF-8/MWCNT-coated quartz crystal microbalance (QCM) sensor successfully detected these volatile organic compounds (VOCs) at 0.62 parts-per-million (ppm) under ambient conditions, a marked improvement over ZIF-8 alone. However, selectivity towards acetone, a crucial biomarker for diabetes, is lacking when other VOCs are present. This study investigates the effect of different sensing platforms with varying response mechanisms on achieving high selectivity for acetone using a ZIF-8/MWCNT-coated QCM and a chemiresistive sensor. The chemiresistive-sensor demonstrated excellent acetone detection performance, with high selectivity, low humidity response, good repeatability, complete reversibility, and rapid response. Remarkably, it achieved a limit of detection of 1.7 parts-per-billion (ppb) at ambient conditions, three orders of magnitude lower than the concentration in the exhaled breath of diabetic patients (1.8 ppm). This breakthrough highlights the high potential of the sensor for diabetes diagnosis and monitoring through breath analysis.

279-OR: Placental IGFBP1 Is Associated with Insulin Sensitivity during Pregnancy and Is an Early Biomarker for Gestational Diabetes

Pregnancy is associated with a profound reduction in insulin sensitivity (IS) that contributes to gestational diabetes (GDM), but the placental factors that lower IS in pregnancy are not fully known. We conducted genome-wide RNA sequencing in 450 placenta samples from a prospective pregnancy cohort (Gen3G). Participants provided plasma samples in the 1st trimester and completed 75g oral glucose tolerance tests in the late 2nd trimester, from which IS was estimated via the Matsuda index. We used regression analyses to test differential expression of 15,232 placental genes related to maternal IS, adjusting for gestational age at delivery, fetal sex, maternal age, gravidity, BMI, and 37 surrogate variables (to account for technical variability). Among the top differentially expressed genes, lower placental expression of IGFBP1 was significantly associated with lower maternal IS (P=1.7×10-4). In 837 Gen3G women, lower IGFPB1 circulating protein was strongly associated with lower IS (r=0.50, P<0.001) and predicted GDM risk (1st trimester median levels: 23,884 pg/mL in no GDM vs 14,363 pg/mL in GDM, adjusted OR=0.55 [0.39-0.75] per quartile increase; P=1.5×10-4). The association between plasma IGFBP1 and IS was replicated in two pregnancy cohorts: SPRING (n=165 with GDM risk factors, r=0.54, P<0.001) and MOMS (n=97 matched GDM cases and controls, r=0.55, P<0.001). The association of lower plasma IGFBP1 with greater risk of GDM was replicated in SPRING (adjusted OR=0.66 per quartile increase, P=0.07) and MOMS (adjusted OR=0.45 per quartile increase, P<0.001). In SPRING, plasma IGFBP1 protein were markedly elevated in the 1st and 2nd trimesters compared to postpartum (P<0.001), consistent with placental origin. Our results suggest that the placenta expresses high levels of IGFBP1, which influences IGF-1 bioavailability and is released in maternal circulation to regulate IS in pregnancy, highlighting it as a promising early plasma biomarker of GDM risk. Disclosure M.Hivert: None. S.Karumanchi: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health. F.White: None. C.Allard: None. K.James: None. S.Majid: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck & Co., Inc. A.Edlow: Consultant; Mirvie, Inc, Research Support; Merck & Co., Inc. L.Bouchard: None. P.Jacques: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD094150)

Fabricating a rapid and low-cost electrochemical biosensor with imprints of glycated albumin molecules to detect diabetes using bimetallic Au-Pt nanoparticles on μSPE

Diabetes is a primary factor that is accountable for health problems and results in millions of deaths. 4 million deaths approximately occurred due to diabetes every year and about 170 million people are suffering universally. For diabetes, no treatment is present that promises to cure this condition. Only blood glucose monitoring is recommended for diabetics. Regular and close monitoring of glucose levels can help to avoid further serious problems. Determining the level of glucose in the blood is an important requirement. This is done by monitoring the levels of glycated hemoglobin (HbA1c), which is a biomarker for glucose. But HbA1c monitoring is unreliable in the presence of certain medical conditions. In such cases another biomarker glycated albumin (GA) is used for glucose monitoring as it remains unaffected by such conditions. As a result, a bimetallic nanomaterial-based sensitive platform was created. This research focuses on the development of a biosensor that utilizes micro-screen printed electrodes (μSPE). The platform was designed to measure the level of GA and demonstrated the synergistic effects of bi-metallic gold-platinum (Au-Pt) nanomaterial. Additionally, the electrochemical response of mono-metallic and bi-metallic nanoparticles was investigated in order to detect glycated albumin, a diabetes biomarker. The biosensor constructed using bimetallic nanoparticles exhibits a broad range of concentrations, lower limit of detection, heightened sensitivity, and selectivity.

Binding of Apo and Glycated Human Serum Albumins to an Albumin-Selective Aptamer-Bound Graphene Quantum Dot Complex.

Diabetes mellitus is a chronic metabolic disease involving continued elevated blood glucose levels. It is a leading cause of mortality and reduced life expectancy. Glycated human serum albumin (GHSA) has been reported to be a potential diabetes biomarker. A nanomaterial-based aptasensor is one of the effective techniques to detect GHSA. Graphene quantum dots (GQDs) have been widely used in aptasensors as an aptamer fluorescence quencher due to their high biocompatibility and sensitivity. GHSA-selective fluorescent aptamers are first quenched upon binding to GQDs. The presence of albumin targets results in the release of aptamers to albumin and consequently fluorescence recovery. To date, the molecular details on how GQDs interact with GHSA-selective aptamers and albumin remain limited, especially the interactions of an aptamer-bound GQD (GQDA) with an albumin. Thus, in this work, molecular dynamics simulations were used to reveal the binding mechanism of human serum albumin (HSA) and GHSA to GQDA. The results show the rapid and spontaneous assembly of albumin and GQDA. Multiple sites of albumins can accommodate both aptamers and GQDs. This suggests that the saturation of aptamers on GQDs is required for accurate albumin detection. Guanine and thymine are keys for albumin-aptamer clustering. GHSA gets denatured more than HSA. The presence of bound GQDA on GHSA widens the entrance of drug site I, resulting in the release of open-chain glucose. The insight obtained here will serve as a base for accurate GQD-based aptasensor design and development.

Structural and Dynamic Alteration of Glycated Human Serum Albumin in Schiff Base and Amadori Adducts: A Molecular Simulation Study.

Human serum albumin (HSA) is a protein carrier in blood transporting metabolites and drugs. Glycated HSA (GHSA) acts as a potential biomarker for diabetes. Thus, many attempts have been made to detect GHSA. Glycation was reported to damage the structure and ligand binding capability, where no molecular detail is available. Recently, the crystal structure of GHSA has been solved, where two glucose isomers (pyranose/GLC and open-chain/GLO) are located at Sudlow's site I. GLO was found to covalently bind to K195, while GLC is trapped by noncontact interactions. GHSA exists in two forms (Schiff base (SCH) and Amadori (AMA) adducts), but how both disrupt albumin activity microscopically remains unknown. To this end, molecular dynamics simulations were performed here to explore the nature of SCH and AMA. Both forms are found to alter the main protein dynamics, resulting in (i) the widening of Sudlow's site I entrance, (ii) the size reduction of nine fatty acid-binding pockets, (iii) the enlargement of Sudlow's site I and the shrinking of Sudlow's site II, (iv) the enhancement of C34 reactivity, and (v) the change in the W214 microenvironment. These unique characteristics found here can be useful for understanding the effect of glycation on the albumin function in more detail and designing specific and selective GHSA detection strategies.

Single-metal (Cu, Ag, Au) encapsulated gallium nitride nanotube (GaNNT) as glucose nonenzymatic nanosensors for monitoring diabetes: Perspective from DFT, visual study, and MD simulation

Developing a diabetes biomarker detector would benefit both current and potential diabetes patients. Therefore, in this present study, metals (Ag, Au, and Cu) doped gallium nitride nanotube (GaNNT) were designed and simulated for the monitoring of diabetes via its biomarkers: alpha-D-glucose (α-DGlu) and beta-D-glucose (β-DGlu) within the framework of first-principles density functional theory (DFT) method at the B3LYP-D3(BJ)/def2-SVP level of theory. Our calculations show that in the gas phase, α-DGlu is best adsorbed on the Au@GaNNT surface with an adsorption energy of −1.812 eV, while β-DGlu adsorbs best on Ag@GaNNT surface, having an adsorption energy of −6.736 eV. In the aqueous phase, comparable Eads values were obtained on the adsorption of β-DGlu. However, β-Au@GaNNT produced an Eads of −6.098 eV, which is higher than others. α-DGlu, on the other hand, was best adsorbed in Au@GaNNT with an Eads of −1.815 eV. The results of the adsorption energy calculations and the calculated recovery time are in good agreement, which suggests that studied nanotubes can be employed as reusable sensors. As a result, considered surfaces provide excellent candidates for the detection of diabetes.

Sucrose Intake Elevates Erythritol in Plasma and Urine in Male Mice

BackgroundElevated serum erythritol concentration is a predictive biomarker of diabetes and cardiovascular incidence and complications. Erythritol is synthesized endogenously from glucose, but little is known regarding the origin of elevated circulating erythritol in vivo. ObjectivesIn vitro evidence indicates that intracellular erythritol is elevated by high-glucose cell culture conditions and that final step of erythritol synthesis is catalyzed by the enzymes sorbitol dehydrogenase (SORD) and alcohol dehydrogenase (ADH) 1. The purpose of this study was to determine whether dietary intake and/or diet-induced obesity affect erythritol synthesis in mice and whether this relationship is modified by the loss of the enzymes SORD or ADH1. MethodsFirst, 8-wk-old male Sord+/+, Sord−/−, Adh1+/+, and Adh1−/− mice were fed either low-fat diet (LFD) with 10% fat-derived calories or diet-induced obesity high-fat diet (HFD) with 60% fat-derived calories for 8 wk. Plasma and tissue erythritol concentrations were measured using gas chromatography–mass spectrometry. Second, male wild-type 8-wk-old C57BL/6J mice were fed LFD or HFD with plain drinking water or 30% sucrose water for 8 wk. Blood glucose and plasma and urinary erythritol concentrations were measured in nonfasted and fasted samples. Tissue erythritol was measured after killing. Finally, male Sord+/+ and Sord−/− mice were fed LFD with 30% sucrose water for 2 wk; then, nonfasted plasma, urine, and tissue erythritol concentrations were quantified. ResultsPlasma and tissue erythritol concentrations were not affected by loss of Sord or Adh1 in mice fed LFD or HFD. In wild-type mice, consumption of 30% sucrose water significantly elevated plasma and urinary erythritol concentrations on both LFD-fed and HFD-fed mice compared with that of plain water. Sord genotype did not affect plasma or urinary erythritol concentration in response to sucrose feeding, but Sord−/− mice had reduced kidney erythritol content compared with wild-type littermates in response to sucrose. ConclusionsSucrose intake, not HFD, elevates erythritol synthesis and excretion in mice. Loss of ADH1 or SORD does not significantly affect erythritol concentration in mice.

Endocan in prediabetes, diabetes, and diabetes-related complications: a systematic review and meta-analysis

BackgroundDiabetes is one of the chronic conditions with a high burden all around the world. Macrovascular and microvascular involvement are among the common mechanisms by which diabetes can impact patients’ lives. Endocan as an inflammatory endothelial biomarker has been shown to increase in several communicable and non-communicable diseases. Herein, we aim to investigate the role of endocan as a biomarker in diabetes as a systematic review and meta-analysis.MethodsInternational databases, including PubMed, Web of Science, Scopus, and Embase were searched for relevant studies assessing blood endocan in diabetic patients. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of circulating endocan levels between diabetic patients and non-diabetic controls were conducted through random-effect meta-analysis.ResultsTotally, 24 studies were included, assessing 3354 cases with a mean age of 57.4 ± 8.4 years. Meta-analysis indicated that serum endocan levels were significantly higher in diabetic patients in comparison with healthy controls (SMD 1.00, 95% CI 0.81 to 1.19, p-value < 0.01). Moreover, in the analysis of studies with only type-2 diabetes, the same result showing higher endocan was obtained (SMD 1.01, 95% CI 0.78 to 1.24, p-value < 0.01). Higher endocan levels were also reported in chronic diabetes complications such as diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy.ConclusionBased on our study’s findings, endocan levels are increased in diabetes, however, further studies are needed for assessing this association. In addition, higher endocan levels were detected in chronic complications of diabetes. This can help researchers and clinicians in recognizing disease endothelial dysfunction and potential complications.

DNA methylation markers for kidney function and progression of diabetic kidney disease

Epigenetic markers are potential biomarkers for diabetes and related complications. Using a prospective cohort from the Hong Kong Diabetes Register, we perform two independent epigenome-wide association studies to identify methylation markers associated with baseline estimated glomerular filtration rate (eGFR) and subsequent decline in kidney function (eGFR slope), respectively, in 1,271 type 2 diabetes subjects. Here we show 40 (30 previously unidentified) and eight (all previously unidentified) CpG sites individually reach epigenome-wide significance for baseline eGFR and eGFR slope, respectively. We also develop a multisite analysis method, which selects 64 and 37 CpG sites for baseline eGFR and eGFR slope, respectively. These models are validated in an independent cohort of Native Americans with type 2 diabetes. Our identified CpG sites are near genes enriched for functional roles in kidney diseases, and some show association with renal damage. This study highlights the potential of methylation markers in risk stratification of kidney disease among type 2 diabetes individuals.

Relationship between cathepsin K and total oxidative state in diabetes mellitus female patients with osteoporosis in Iraq

Introduction and Aim: Diabetes mellitus patients almost always struggle with a metabolic condition known as chronic hyperglycemia. According to the World Health Organization, osteoporosis is a progressive systemic skeletal disorder that is characterized by decreasing bone mass and microstructural breakdown of bone tissue that increases susceptibility to fracture and increased risk of breaking a bone. Here, we aimed to compare the levels of CatK and total oxidative state in patients with diabetes and osteoporosis among the female Iraqi population and study the possible relationship between them. Materials and Methods: This study included 40 females with diabetes (Group G1), 40 with diabetes and osteoporosis (Group G2) and 40 normal healthy females (Group G3) as controls. All participants were checked for their height, weight and BMI. Blood drawn from everyone was analyzed for fasting blood sugar, HbA1c, Cathepsin K, TOS, TAC and MDA. Data obtained was subjected to statistical analysis. Results: According to the findings, the levels of cathepsin K increased significantly (P 0.001) from Group 1 to Groups 2 and 3, as measured by their mean and standard deviation values. The results of total oxidant status, expressed as means and standard deviations (Mean SD), demonstrated a high significant (P 0.001) decline from group G1 to groups G2 and G3. Conclusion: Cathepsin K was observed to be linked to both type 2 diabetes and bone loss. In postmenopausal Iraqi women with type 2 diabetes, Cathepsin K may serve as a biomarker for both diabetes and osteoporosis.

Development of a novel method for analysing N-acetyl-DL-leucine enantiomers in human fingernail by UPLC-ESI-MS/MS and the evaluation in diabetes mellitus

BackgroundRecent research has been reported that N-acetyl-leucine content is significantly reduced in the saliva of diabetic patients, but no reports of detection in human nails have been found. This study aims to develop a novel method for the chiral separation of N-acetyl-DL-leucine (Ac-DL-Leu) in human fingernails to investigate the differences between healthy volunteers (HVs), prediabetes (PDs) and diabetic patients (DPs), and to verify its effectiveness in early warning of diabetes. MethodChiral resolution was performed using DBD-Apy pre-column derivatization on a C18 column (2.1 × 150 mm, 1.9 μm) at 40 °C, and detected by UPLC-ESI-MS/MS. ResultsThe resolution and the limit of detection (LOD) of Ac-DL-Leu were 1.75 and 1.50 fmol, respectively. The linear range of Ac-DL-Leu was 10–2000 fmol and the determination coefficient (R2) was above 0.9997. The recovery of Ac-DL-Leu in human nails was 96.92–105.69 %. The contents of Ac-D-Leu and Ac-L-Leu were analyzed in 18 HVs, 13 PDs and 16 DPs fingernails. The results showed that their contents were significantly lower in DPs than in PDs and HVs (p < 0.0001). ConclusionsA method for evaluating the effectiveness of Ac-DL-Leu enantiomers in human fingernails as a biomarker for diabetes was firstly developed.

Clinical Manifestations and Biomarkers of the Maturity-Onset Diabetes of the Young

Clinical Manifestations and Biomarkers of the Maturity-Onset Diabetes of the Young

Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus.

The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81). Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.

Glycemia-Induced miRNA Changes: A Review.

Diabetes is a rapidly increasing global health concern that significantly strains the health system due to its downstream complications. Dysregulation in glycemia represents one of the fundamental obstacles to achieving glycemic control in diabetic patients. Frequent hyperglycemia and/or hypoglycemia events contribute to pathologies that disrupt cellular and metabolic processes, which may contribute to the development of macrovascular and microvascular complications, worsening the disease burden and mortality. miRNAs are small single-stranded non-coding RNAs that regulate cellular protein expression and have been linked to various diseases, including diabetes mellitus. miRNAs have proven useful in the diagnosis, treatment, and prognosis of diabetes and its complications. There is a vast body of literature examining the role of miRNA biomarkers in diabetes, aiming for earlier diagnoses and improved treatment for diabetic patients. This article reviews the most recent literature discussing the role of specific miRNAs in glycemic control, platelet activity, and macrovascular and microvascular complications. Our review examines the different miRNAs involved in the pathological processes leading to the development of type 2 diabetes mellitus, such as endothelial dysfunction, pancreatic beta-cell dysfunction, and insulin resistance. Furthermore, we discuss the potential applications of miRNAs as next-generation biomarkers in diabetes with the aim of preventing, treating, and reversing diabetes.

Interactions of BDNF Val66met and dietary indices in relation to metabolic markers among patient with type 2 diabetes mellitus: a cross-sectional study

BackgroundGene–diet interaction is related to the progression of diabetes and cardiovascular diseases biomarkers. We aimed to evaluate the interaction between diet quality indices and BDNF Val66Mat (rs6265) on cardiometabolic markers among diabetic patients.MethodsThis cross-sectional study was conducted on 634 patients with type 2 diabetes mellitus, which were randomly recruited from diabetic centers in Tehran. Dietary intakes were estimated by a previously validated semi-quantitative food frequency questionnaire comprising 147 items. All participants were categorized into three categories, based on healthy eating index (HEI), diet quality index (DQI), and phytochemical index (PI) scores. Polymerase chain reaction was used for genotyping the BDNF Val66Met. Interactions were tested using analysis of covariance in adjusted and crude models.ResultsOur result showed that higher DQI, HEI, and PI scores significantly decrease body mass index and waist circumference among individuals with Met/Met, Val/Met, and Val/Val genotypes (P interactions < 0.05). Moreover, the highest quartile of the DQI and PI, compared to the lowest, showed lower TG level among Met allele carriers compared to Val/Val homozygotes (P interaction = 0.004 and 0.01, respectively) and a faster reduction in IL-18 and TC level was seen among Met/Met, Val/Met who had higher HEI intake than those with Val/Val genotype.ConclusionsBDNF Val66Met polymorphism may interact with HEI, DQI, and PI. We have revealed that Met allele acts as a protective allele for diabetic patients and may have a beneficial influence on cardio-metabolic factors through regulating dietary intake.

Urinary metabolomics of phenolic compounds reveals biomarkers of type-2 diabetes within the PREDIMED trial

BackgroundPhenolic compounds have been associated with protective effects against type-2 diabetes (T2D). We used a metabolomics approach to determine urinary phenolic metabolites associated with T2D and fasting plasma glucose. MethodsThis case-control study within the PREDIMED trial included 200 participants at high cardiovascular risk, 102 of whom were diagnosed with T2D. A panel of urinary phenolic compounds were analysed using a novel method based on liquid chromatography coupled to mass spectrometry. Multivariate statistics and adjusted logistic regressions were applied to determine the most discriminant compounds and their association with T2D. The relationship between the discriminant phenolic compounds and plasma glucose was assessed using multivariable linear regressions. ResultsA total of 41 phenolic compounds were modeled in the orthogonal projection to latent structures discriminant analysis, and after applying adjusted logistic regressions two were selected as discriminant: dihydrocaffeic acid (OR = 0.22 (CI 95 %: 0.09; 0.52) per 1-SD, p-value = 0.021) and genistein diglucuronide (OR = 0.72 (CI 95%: 0.59; 0.88) per 1-SD, p-value = 0.021). Both metabolites were associated with a lower risk of suffering from T2D, but only dihydrocaffeic acid was inversely associated with plasma glucose (β = −17.12 (95 % CI: −29.92; −4.32) mg/dL per 1-SD, p-value = 0.009). ConclusionsA novel method using a metabolomics approach was developed to analyse a panel of urinary phenolic compounds for potential associations with T2D, and two metabolites, dihydrocaffeic acid and genistein diglucuronide, were found to be associated with a lower risk of this condition.

Association of circulatory PCSK-9 with biomarkers of redox imbalance and inflammatory cascades in the prognosis of diabetes and associated complications: a pilot study in the Indian population

s Besides the profound role of proprotein convertase subtilisin/kexin type-9 (PCSK-9) in LDL-C regulation, its association with other metabolic complications cannot be disregarded. The co-existence of redox imbalance and inflammatory cascades has greatly reflected the etiology of hyperglycemia. Therefore, we studied the association of PCSK-9 with inflammation and oxidative stress biomarkers to predict its role in the prognosis of diabetes and its associated complications in the Indian population. This pilot study examined a total of n = 187 subjects: healthy controls (HC; n = 50), diabetic without complication (T2DM; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemic (T2DM-DL; n = 45) subjects. The relationship between circulatory PCSK-9 levels and inflammation and redox imbalance biomarkers has been explored. The significant positive association of elevated PCSK-9 level with the inflammatory (i.e. IL-1β, IL-6, TNF-α, and CRP) and oxidative stress marker (i.e. XOD, CD, LOOH, and MDA) was observed in T2DM-N and T2DM-DL subjects. Whereas single regression analysis depicted that PCSK-9 was inversely associated with the FRAP and PON-1 in T2DM-N and T2DM-DL subjects. Furthermore, no significant correlation was detected in both T2DM and HC subjects. We found a significant relationship between these prognostic biomarkers with an elevated level of PCSK-9 in T2DM-N and T2DM-DL subjects. PCSK-9 is a nontraditional biomarker in diabetes that may help identify patients at risk of developing secondary complications of diabetes in the Indian population. However, further large cohort validation studies are needed.

351 Trends Between Periodontitis and Medial Arterial Calcification in Undiagnosed Type II Diabetes Mellitus

OBJECTIVES/GOALS: The overall objective of this study is to determine if medial arterial calcification (MAC) is an independent predictor of diabetes and to evaluate the relationship between MAC, periodontitis and Type II diabetes mellitus. METHODS/STUDY POPULATION: A retrospective case-control model analyzing radiographs for periodontitis and MAC to identify potential biomarkers for underlying systemic conditions, such as diabetes. Charts of patients attending UPENN School of Dental Medicine clinics between 2015 and 2022 were reviewed. Demographics, medical and dental history, diabetic status (identified by POC blood glucose level, fasting blood glucose and/or A1C), and medication history were documented amongst other variables. Patients aged 18 years or older with diabetes and having full mouth intraoral radiographs (FMX), panoramic radiographs and CBCTs were included. Patients with radiographs of poor quality were excluded. Multivariate analysis was used to determine possible associations between diabetes and periodontitis among persons with or without MAC. RESULTS/ANTICIPATED RESULTS: In our pilot study involving 28 participants, 53% of the population with moderate or severe periodontitis had MAC. By the Fisher’s Exact Test, there was an association, meaning those with more periodontal disease are more likely to have MAC (p=0.014). Sixty-three percent of patients with diabetes had MAC, while 19% of patients without evidence of diabetes also had MAC, (p=0.067). There was not enough evidence of association between diabetes and presence of MAC at this time, due to a small sample size, however there was a high prevalence of MAC among the diabetics. We hypothesized that periodontitis, a condition that shares many risk factors with diabetes would also be associated with incident MAC. Findings from this study will be key for the implementation of preventive screening protocols and referral systems. DISCUSSION/SIGNIFICANCE: Diabetes is on the rise and about half of diabetics are undiagnosed. CBCT imaging frequently used in dentistry can detect incidental findings such as MAC. This study has the potential of detecting statistically significant links between MAC, periodontitis and diabetes, hence serving as a sensitive radiographic biomarker for diabetes.