Background 
Metabolomics is the rapidly evolving field of the comprehensive measurement of ideally all endogenous metabolites in a biological fluid. However, no single analytic technique covers the entire spectrum of the human metabolome. Here we present results from a multiplatform study, in which we investigate what kind of results can presently be obtained in the field of diabetes research when combining metabolomics data collected on a complementary set of analytical platforms in the framework of an epidemiological study.


Methodology/Principal Findings 
40 individuals with self-reported diabetes and 60 controls (male, over 54 years) were randomly selected from the participants of the population-based KORA (Cooperative Health Research in the Region of Augsburg) study, representing an extensively phenotyped sample of the general German population. Concentrations of over 420 unique small molecules were determined in overnight-fasting blood using three different techniques, covering nuclear magnetic resonance and tandem mass spectrometry. Known biomarkers of diabetes could be replicated by this multiple metabolomic platform approach, including sugar metabolites (1,5-anhydroglucoitol), ketone bodies (3-hydroxybutyrate), and branched chain amino acids. In some cases, diabetes-related medication can be detected (pioglitazone, salicylic acid).


Conclusions/Significance 
Our study depicts the promising potential of metabolomics in diabetes research by identification of a series of known and also novel, deregulated metabolites that associate with diabetes. Key observations include perturbations of metabolic pathways linked to kidney dysfunction (3-indoxyl sulfate), lipid metabolism (glycerophospholipids, free fatty acids), and interaction with the gut microflora (bile acids). Our study suggests that metabolic markers hold the potential to detect diabetes-related complications already under sub-clinical conditions in the general population.

/pdf/metabolic-footprint-of-diabetes-a-multiplatform-metabolomics-4lmbarm42e.pdf

Metabolic footprint of diabetes: a multiplatform metabolomics study in an epidemiological setting.

This randomized trial tested whether twice-daily exenatide reduces hemoglobin A1c levels more than placebo in people with type 2 diabetes who are receiving insulin glargine. After 30 weeks, exenati...

Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial.

Efficacy and safety of sitagliptin monotherapy in Japanese patients with type 2 diabetes.

Content: Recent studies have reported hemoglobin A1c (A1c) differences across racial/ethnic groups. Our diverse population allows for further investigation of potential differences in measurements of glycemia. Objectives: Our objectives were to describe and explore baseline racial/ethnic differences in self-monitored plasma glucose profiles, A1c, and 1,5-anhydroglucitol (1,5-AG) in patients with type 2 diabetes enrolled in the Assessing DURAbility of Basal vs. Lispro Mix 75/25 Insulin Efficacy trial. Design, Setting, Patients: The trial enrolled 2094 patients with type 2 diabetes, ages 30–80 yr, from 11 countries. Main Outcome Measures: Estimated mean plasma glucose (MPG), A1c, and 1,5-AG were compared among racial/ethnic groups before and after adjusting for factors affecting glycemia: age, sex, duration of diabetes, body mass index, and MPG. Results: Baseline estimated MPG ± sd was 220.0 ± 82.0 mg/dl, mean A1c was 9.0 ± 1.3%, and 1,5-AG was 5.0 ± 4.1μg/ml. Estimated MPG did not differ between Caucasian ...

/pdf/racial-and-ethnic-differences-in-mean-plasma-glucose-2398shbmyc.pdf

Racial and ethnic differences in mean plasma glucose, hemoglobin A1c, and 1,5-anhydroglucitol in over 2000 patients with type 2 diabetes.

1,5-anhydroglucitol (1,5-AG) is a validated marker of short-term glycemic control. It is a metabolically inert polyol that competes with glucose for reabsorption in the kidneys. Otherwise stable levels of 1,5-AG are rapidly depleted as blood glucose levels exceed the renal threshold for glucosuria. 1,5-AG more accurately predicts rapid changes in glycemia than hemoglobin A1C (A1C) or fructosamine. It is also more tightly associated with glucose fluctuations and postprandial glucose. Thus, 1,5-AG may offer complementary information to A1C. This review will summarize the limitations of current methods of assessing glycemic control, assess the data to support 1,5-AG as a glycemic marker and highlight the scenarios by which 1,5-AG may fill the gap in assessing glycemic control.

1,5-anhydroglucitol (GlycoMark) as a marker of short-term glycemic control and glycemic excursions.

OBJECTIVE —Postprandial hyperglycemia is often inadequately assessed in diabetes management. Serum 1,5-anhydroglucitol (1,5-AG) drops as serum glucose rises above the renal threshold for glucose and has been proposed as a marker for postprandial hyperglycemia. The objective of this study is to demonstrate the relationship between 1,5-AG and postprandial hyperglycemia, as assessed by the continuous glucose monitoring system (CGMS) in suboptimally controlled patients with diabetes. RESEARCH DESIGN AND METHODS —Patients with type 1 or type 2 diabetes and an HbA 1c (A1C) between 6.5 and 8% with stable glycemic control were recruited from two sites. A CGMS monitor was worn for two consecutive 72-h periods. Mean glucose, mean postmeal maximum glucose (MPMG), and area under the curve for glucose above 180 mg/dl (AUC-180), were compared with 1,5-AG, fructosamine (FA), and A1C at baseline, day 4, and day 7. RESULTS —1,5-AG varied considerably between patients (6.5 ± 3.2 μg/ml [means ± SD]) despite similar A1C (7.3 ± 0.5%). Mean 1,5-AG ( r = −0.45, P = 0.006) correlated with AUC-180 more robustly than A1C ( r = 0.33, P = 0.057) or FA ( r = 0.38, P = 0.88). MPMG correlated more strongly with 1,5-AG ( r = −0.54, P = 0.004) than with A1C ( r = 0.40, P = 0.03) or FA ( r = 0.32, P = 0.07). CONCLUSIONS —1,5-AG reflects glycemic excursions, often in the postprandial state, more robustly than A1C or FA. 1,5-AG may be useful as a complementary marker to A1C to assess glycemic control in moderately controlled patients with diabetes.

https://care.diabetesjournals.org/content/diacare/29/6/1214.full.pdf

1,5-anhydroglucitol and postprandial hyperglycemia as measured by continuous glucose monitoring system in moderately controlled patients with diabetes.

Objective: 1, 5-anhydroglucitol (1,5-AG) is a short-term marker of metabolic control in diabetes. Its renal loss is stimulated in hyperglycemic conditions by glycosuria, which results in lowered plasma concentration. As low renal threshold for glucose has been described in HNF-1α MODY, 1,5-AG level may be altered in these patients. The purpose of this study was to assess the 1,5-AG levels in HNF-1α MODY patients and in type 2 diabetes (T2DM) subjects with a similar degree of metabolic control. In addition, we aimed to evaluate this particle as a biomarker for HNF-1α MODY. Research Design and Methods: We included 33 diabetic patients from the Polish Nationwide Registry of MODY. In addition, we examined 43 T2DM patients and 47 non-diabetic controls. 1,5-AG concentration was measured with an enzymatic assay (GlycoMark). The ROC (receiver operation characteristic) analysis was utilized to evaluate 1,5-AG as a screening marker for HNF-1α MODY. Results: The mean 1, 5-AG plasma concentration in diabetic HNF-1α mutation carriers was 5.9 μg/ml and it was lower than in T2DM patients (11.0 μg/ml, p=0.003), and in non-diabetic controls (23.9 μg/ml, p 1c level between 6.5% and 9.0%. Conclusions: 1, 5-AG may be a useful biomarker for differential diagnosis of HNF-1α MODY patients with a specific range of HbA 1c , although it requires further investigation. However, the clinical use of this particle in diabetic HNF-1α mutation carriers for metabolic control has substantial limitations.

https://care.diabetesjournals.org/content/diacare/31/8/1496.full.pdf

Clinical Application of 1,5-Anhydroglucitol Measurements in Patients with Hepatocyte Nuclear Factor-1α Maturity-Onset Diabetes of the Young

Described herein is a method for determining the disease state in a patient using combined mean glucose measurements and 1,5-anhydroglucitoi to identify individuals at risk for developing diabetes. The ratio of mean glucose measurements to 1,5-anhydroglucitol correlates significantly better to maximal levels of postmeal glucose levels and related measurements, than mean glucose measurements or 1,5-anhydroglucitol correlate independent!y.

Improved identification of pre-diabetes using a combination of mean glucose and 1,5-anhydroglucitol markers

The invention is a method of measuring blood glucose excursions in general, and postprandial hyperglycemia in diabetic patients in particular, by the 1,5-anhydroglucitol assay (1,5-AG) or A1C/1,5-AG assay combination. 1,5-AG levels and percent changes of 1,5-AG levels in short period are indicative of differing postmeal glucose levels in moderately-controlled diabetic patients with similar AlC levels. Thereby 1,5-AG assay is useful to identify diabetic patients who may be at risk for cardiovascular complications which would not be identifiable by AlC levels alone. Furthermore, ratios of AlC divided by 1,5-AG in each patient are superior indicators to 1,5-AG levels.

The 1, 5-anhydroglucitol (1, 5-ag) assay and a1c/1. 5-ag assay combination for measuring blood glucose excursions in general and postprandial hyperglycemia in diabetic patients

HbA1c measurement is a critical component of diabetes management; however, a key limitation of HbA1c as a measure of glycemia is the lack of timeliness -- it does not detect underlying blood glucose excursion levels in moderately controlled diabetic patients (HbA1c < 8) as it is a measurement of mean glucose levels over the longer-term HbA1c also averages both hypo- and hyperglycemia over two to three months; therefore, it does not adequately reflect improvements in post-prandial hyperglycemia 1,5-AG is also a marker of glycemic control over a shorter one to two week timeframe, but with a different mechanism than HbA1c Given the unique biological and physiological characteristics of 1,5-AG, it is sensitive to acute and transient episodes of hyperglycemia and is, therefore, a better indicator of glucose excursions Peptidyl diabetic drugs such as pramlintide and exenatide have unique mechanisms of action and the glycemic effects of these drugs are not adequately shown by HbA1c 1,5-AG, an effective measure of glucose excursions, reveals underlying treatment effects of these drugs and can help regulate their dosage

Method to monitor drug efficacy in diabetic patients using an assay for 1,5-anhydro-d-glucitol

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Eric A. Button

Author Tools

Chat about Author