Int J Med Sci. 2016 Jan 1;13(1):25-38.

Abstract
INTRODUCTION:
Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia.
METHODS:
A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1).
RESULTS:
According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster.
CONCLUSION:
Based on the evidence presented within the literature, the aforementioned biomarkers correlate significantly with metabolic syndrome and could provide a minimally-invasive means for early detection and specific treatment of these disorders. Further research is encouraged to determine the efficacy of applying these biomarkers to diagnosis and treatment in a clinical setting.

Clinical Chemistry December 2012 vol. 58 no. 12 1615-1617

The underlying pathophysiology of diabetes varies, but all patients share a common a metabolic derangement of carbohydrate metabolism, which causes hyperglycemia. Many patients with diabetes develop debilitating complications, ranging from retinopathy and nephropathy, to myocardial infarction and stroke. The accumulated evidence reveals that reducing an increased glucose concentration, as documented by a lower hemoglobin A1c (Hb A1c)4 concentration, decreases complications (1, 2). Hb A1c is extensively used to monitor glycemic control and to adjust therapy, and it has recently been accepted as a criterion for the diagnosis of diabetes (3).

Hb A1c reflects long-term glycemia, because glucose attaches irreversibly (the process is termed glycation) to hemoglobin in erythrocytes. Hb A1c can be modified independently of glycemia, however, by conditions (e.g., anemia or renal failure) that alter the mean age of erythrocytes by changing either their production or their rate of disappearance. Recent observations have revealed that the life span of erythrocytes in healthy individuals who have normal blood counts and indices can vary sufficiently from the commonly taught 120 days to cause clinically relevant differences in Hb A1c concentrations (4). These limitations have led to investigations of an expanding group of alternative markers of glycemia.

The best studied of these analytes is fructosamine, which is the generic name for plasma protein ketoamines. Because albumin is the most abundant protein in serum, fructosamine is predominantly a measure of glycated albumin. The covalent attachment of glucose to albumin forms glycated albumin, which can also be assayed directly (5). The half-life of albumin in the blood is 14–20 days, so both fructosamine and glycated albumin indicate the mean blood glucose concentration over the preceding 2 weeks. The fructosamine assay was developed in 1983 (6), but it was modified—and improved—in 1990 by the addition of uricase, a nonionic detergent, and polylysine calibrators (7). Automated assays of glycated albumin have been available for approximately 10 years. Fructosamine and glycated albumin are extracellular and have several useful attributes, including independence from both erythrocyte life span and glucose transport across membranes. The assays are rapid, technically easy, and inexpensive; however, changes in protein concentration and half-life affect fructosamine, and whether the results need to be corrected for albumin concentration remains controversial. Glycated albumin is also altered by conditions other than glycemia, including the nephrotic syndrome, thyroid dysfunction, hepatic cirrhosis, smoking, hyperuricemia, and hypertriglyceridemia (5).

Another indicator of glycemia is 1,5-anhydroglucitol (1,5-AG), a 6-carbon monosaccharide that is not metabolized (8). Because glucose in the urine competes for reabsorption of 1,5-AG by the kidneys, blood glucose concentrations that exceed the renal threshold [usually approximately 180 mg/dL (10 mmol/L)] reduce the circulating 1,5-AG. The clinical value of 1,5-AG as a marker of short-term glycemia, especially the postprandial glucose concentration, is limited by other factors that modify 1,5-AG, including diet, sex, and renal impairment (8). Although several assays for these alternative markers are commercially available, these analytes all suffer from a major deficiency: clinical studies have been limited, and there is a paucity of rigorous analysis in the literature. For example, the number of PubMed hits in humans for fructosamine, glycated albumin, and 1,5-AG is 3.75%, 2.3%, and 0.35%, respectively, of that for Hb A1c.

Clinical Chemistry January 2013 vol. 59 no. 1 147-157

BACKGROUND: Protein cancer biomarkers serve multiple clinical purposes, both early and late, during disease progression. The search for new and better biomarkers has become an integral component of contemporary cancer research. However, the number of new biomarkers cleared by the US Food and Drug Administration has declined substantially over the last 10 years, raising concerns regarding the efficiency of the biomarker-development pipeline.

CONTENT: We describe different clinical uses of cancer biomarkers and their performance requirements. We also present examples of protein cancer biomarkers currently in clinical use and their limitations. The major barriers that candidate biomarkers need to overcome to reach the clinic are addressed. Finally, the long and arduous journey of a protein cancer biomarker from the bench to the clinic is outlined with an example.

SUMMARY: The journey of a protein biomarker from the bench to the clinic is long and challenging. Every step needs to be meticulously planned and executed to succeed. The history of clinically useful biomarkers suggests that at least a decade is required for the transition of a marker from the bench to the bedside. Therefore, it may be too early to expect that the new technological advances will catalyze the anticipated biomarker revolution any time soon.

Fulltext

Clinicians can use several biochemical measurements to objectively assess patients’ current or past alcohol use. However, none of these currently available biomarkers—including measures of various liver enzymes and blood volume—are ideal. Several more experimental markers hold promise for measuring acute alcohol consumption and relapse. These include certain alcohol byproducts, such as acetaldehyde, ethyl glucuronide (EtG), and fatty acid ethyl esters (FAEE), as well as two measures of sialic acid, a carbohydrate that appears to be altered in alcoholics. Some progress has been made in finding markers that predict people’s genetic predisposition to alcoholism, such as genetic differences in several neurotransmitters, including beta-endorphin and gamma-aminobutryic acid (GABA).

A comparison of some state markers of alcohol consumption. Bars represent approximations, and some variability exists for each marker time period because of individual variability, different test manufacturers, and the like. FAEE = fatty acid ethyl esters, WBAA = whole blood–associated acetaldehyde, CDT = carbohydrate-deficient transferrin, GGT = gamma-glutamyltransferase, MCV = mean corpuscular volume.

Clinical Chemistry January 2012 vol. 58 no. 1 45-53

BACKGROUND: Cardiovascular (CV) clinical trials are instrumental in understanding treatment effects and offer insights into the natural progression of CV disease. Biomarkers are a critical component of patient selection, end point definition, and safety monitoring, and clinical trials provide a platform for the discovery and validation of new biomarkers that may augment the understanding of disease mechanisms, risk stratification, and/or clinical decision-making.

CONTENT: We review the roles that biomarkers have played in CV clinical trials and roles that CV clinical trials have played and will continue to play in the discovery and validation of biomarkers and their implementation in clinical practice. Large biobanks containing multiple specimen types are increasingly being created from patients enrolled in clinical trials, and such biobanks, when coupled with advances in molecular techniques and bioinformatics, promise to accelerate our understanding of CV disease mechanisms and to help fuel the discovery and development of novel therapeutic targets and biomarkers of risk and treatment response.

SUMMARY: The past, present, and future of biomarkers and clinical trials have been and will remain intertwined. Biomarkers were once the workhorses of patient selection and end point definition in clinical trials; more recently, clinical trials have been the proving ground for individual biomarkers. Attention to biobanking and the application of modern informatics and molecular techniques to samples collected within clinical trials will usher in the era of stratified and personalized medicine.

Clinical Chemistry January 2012 vol. 58 no. 1 21-24

I was asked for this special issue to reflect on the area of laboratory tests for identifying cardiac injury. I will include my own experiences in this area, as well as some of others and a bit of personal perspective. I have published elements of this history previously (1–3) and freely admit to drawing on my prior publications.

Considerations for a blood protein biomarker to identify the death of any cell involve 3 major factors: sensitivity, which will be affected by the abundance and location of the protein in the cell; the timing of sampling, which is influenced by the mode of entry into blood and the half-life of elimination; and specificity for the cell of interest. A compounding factor in myocardial infarction (MI)2 (acute coronary syndrome) is that the acute event is caused by blockage of blood flow in a coronary artery or arteries that leads to hypoxia and cell death. This blockage delays protein markers from reaching the blood because they cannot readily diffuse into the blood; instead, they reach the blood via the lymphatics, which is somewhat akin to traveling on city streets rather than on an interstate.

Today, we have several discovery tools for identifying candidate cell injury biomarkers via gene expression (4) or proteomics (5) in a reasonably straightforward manner. It is noteworthy that cardiac biomarkers evolved without such tools, and appropriate biomarkers were found intuitively and empirically (Table 1), probably because the heart’s major function is contraction, which requires energy. The biomarkers used were all involved in energy production or control of contraction.

Archives Medical Review Journal. 2013; 22(2): 221-229

Akut böbrek hasarı glomerüler filtrasyon hızında, hızlı azalma ile beraber üre ve kreatinin gibi nitrojen artık ürünlerinin birikimi, sıvı ve elektrolit, asit ve baz dengesinin bozulması ile kendini gösteren klinik bir sendromdur. Özelikle birkaç komorbid hastalığı olan kişilerde sık görülen ve mortaliteyi artıran önemli bir klinik problemdir. Hastanede yatan hastaların %5’inde, yoğun bakım hastalarının ise %30-50’sinde görülebilmektedir. Halen kullandığımız seri kreatinin ölçümü ve idrar miktarı böbrek hasarının erken tanınmasına olanak vermemektedir. Serum kreatinin düzeyi yaşa, kiloya, hastanın hidrasyon durumuna göre değişkenlik göstermekte ve böbrek hasarı %50 gibi yüksek bir orana ulaşmadıkça artmayabilmektedir. Bu nedenle yeni belirteçlere ihtiyaç duyulmuştur. Bu derlemede, üzerinde en fazla çalışılan belirteçler, nötrofil jelatinaz ilişkili lipokalin, sistain-C, kidney injury molekül-1, liver fatty acid binding proteinler ve IL-18’i gözden geçireceğiz

Mol Biol Rep. 2012 Aug;39(8):8483-90. Epub 2012 Jun 15.

Abstract

The cumulative lifetime risk for the development of colorectal cancer in the general population is 6 %. In many cases, early detection by fecal occult blood test is limited regarding sensitivity. Therefore, there is an urgent need for improved diagnostic tests in colorectal cancer. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers form numerous colorectal cancer protein expression profiling studies. To address the challenge, we have carried out a comprehensive systematic review of colorectal cancer biomarkers from 13 published studies that compared the protein expression profiles of colorectal cancer and normal tissues. A protein ranking system that considers the number of comparisons in agreement, total sample sizes, average fold-change and direction of differential expression was devised. We observed that some proteins were consistently reported by multiple studies as differentially expressed with a statistically significant frequency (P < 0.05) in cancer versus normal tissues comparison. Our systematic review method identified proteins that were consistently reported as differentially expressed. A review of the top four candidates revealed proteins described previously as having diagnostic value as well as novel candidate biomarkers. These candidates should help to develop a panel of biomarkers with sufficient sensitivity and specificity for the diagnosis of colorectal cancer in a clinical setting.

Blood Purif. 2010;29(4):357-65

Abstract
Acute kidney injury (AKI) is a frequent clinical problem in critically ill patients and the associated mortality is high. Standard serum and urine biomarkers are insensitive and nonspecific for the detection of kidney injury in its early stages which limits the therapeutic options and may compromise the outcome. The study presents new candidates for biochemical markers of AKI, with potentially high sensitivity and specificity, causally related to its pathogenesis and development. Some of these biomarkers measured in serum or urine are well known in laboratory practice but have been used in other tests, while some novel biomarkers have been proposed as a result of experimental and clinical studies. In current clinical practice, identification and classification of AKI is based on elevations in serial serum creatinine concentrations, which are delayed and therefore unreliable in the acute setting. The most promising of the new serum AKI markers are cystatin C, neutrophil gelatinase-associated lipocalin and uric acid. Urinary AKI markers may be classified as enzymes released from damaged tubular cells (alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminopeptidase, isoenzymes of glutathione transferase, N-acetyl-beta-D-glucosaminidase), low-molecular-weight proteins (alpha(1)-microglobulin, beta(2)-microglobulin, retinol-binding protein, cystatin C) and proteins specifically produced in the kidney and associated with the development of AKI [cysteine-rich protein 61, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, cytokines and chemokines (Gro-alpha, IL-18), and structural and functional proteins of renal tubules (F-actin, Na(+)/H(+) exchange isoform 3)]. Based on the different expression of these markers, using a panel of serum and urine markers may potentially help to distinguish between various types of insults, establish the duration and severity of injury, predict the clinical outcome and help to monitor response to treatment in AKI.

Circ J. 2010;74(7):1274-82.

Abstract
Chronic kidney disease (CKD) is frequently associated with a progressive decrease in the glomerular filtration rate, which leads to endstage renal disease (ESRD). Heart failure (HF) is a complex syndrome rather than a primary diagnosis, and considered as the endpoint of all cardiovascular disorders. It is the leading cause of death among the cardiovascular diseases in patients with CKD and ESRD. There is some interaction between the heart and kidney (the so-called “cardiorenal syndrome”), and HF patients with the complication of CKD or ESRD show a worse prognosis. Thus, early diagnosis and aggressive management of HF are needed in patients with CKD and ESRD. A number of biomarkers appear to have growing clinical importance and are reported for detection and stratification of HF. Although HF and CKD have a close interrelationship, the utility of the biomarkers has not been adequately studied with regard to the relationship with renal dysfunction. This paper reviews of the current evidence about laboratory biomarkers in patients with HF or CKD, emphasizing the emerging cardiac biomarkers (ie, BNPs and cardiac troponins), and the biomarkers of renal injury (ie, cystatin C and neutrophil gelatinase-associated lipocalin). Furthermore, it discusses the potential role of these markers in terms of heart – kidney interactions and their utility in the diagnostic and therapeutic strategies for cardiorenal syndrome.

JOP. 2010 Nov 9;11(6):536-44.

Abstract
Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those with hereditary pancreatitis and genetic syndromes which predispose to cancer. Ongoing work to identify early markers of pancreas cancer consists of high throughput discovery methods including gene arrays and proteomics as well as hypothesis driven methods. While several promising candidates have been identified none has yet been convincingly proven to be better than CA 19-9. New methods including endoscopic ultrasound are improving detection of pancreas cancer and are being used to acquire tissue for biomarker discovery.

J Clin Pathol. 2006 Apr;59(4):340-4.

Serum amylase remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis, but its sensitivity can be reduced by late presentation, hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen-2 is convenient, of comparable diagnostic accuracy, and provides greater (99%) negative predictive value. Early prediction of the severity of acute pancreatitis can be made by well validated scoring systems at 48 hours, but the novel serum markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography. For obscure aetiologies, serum calcium and triglycerides should be measured. Genetic polymorphisms may play an important role in “idiopathic” acute recurrent pancreatitis.