scholarly journals Metabolic Dysfunction Biomarkers as Predictors of Early Diabetes

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1589
Author(s):  
Carla Luís ◽  
Pilar Baylina ◽  
Raquel Soares ◽  
Rúben Fernandes
Keyword(s):  
Early Stage ◽  
Clinical Manifestations ◽  
Metabolic Dysfunction ◽  
Inclusion Criteria ◽  
Early Diabetes ◽  
Clinical Phase ◽  
Novel Biomarkers ◽  
Metabolic Biomarkers ◽  
New Strategies

During the pathophysiological course of type 2 diabetes (T2D), several metabolic imbalances occur. There is increasing evidence that metabolic dysfunction far precedes clinical manifestations. Thus, knowing and understanding metabolic imbalances is crucial to unraveling new strategies and molecules (biomarkers) for the early-stage prediction of the disease’s non-clinical phase. Lifestyle interventions must be made with considerable involvement of clinicians, and it should be considered that not all patients will respond in the same manner. Individuals with a high risk of diabetic progression will present compensatory metabolic mechanisms, translated into metabolic biomarkers that will therefore show potential predictive value to differentiate between progressors/non-progressors in T2D. Specific novel biomarkers are being proposed to entrap prediabetes and target progressors to achieve better outcomes. This study provides a review of the latest relevant biomarkers in prediabetes. A search for articles published between 2011 and 2021 was conducted; duplicates were removed, and inclusion criteria were applied. From the 29 studies considered, a survey of the most cited (relevant) biomarkers was conducted and further discussed in the two main identified fields: metabolomics, and miRNA studies.

scholarly journals Urinary Exosomal MicroRNA Profiling in Incipient Type 2 Diabetic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yijun Xie ◽  
Yijie Jia ◽  
Xie Cuihua ◽  
Fang Hu ◽  
Meng Xue ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Strong Predictor ◽  
Differentially Expressed ◽  
Diabetic Kidney ◽  
Reverse Transcription Pcr ◽  
Novel Biomarkers ◽  
Renal Failure Fluid

Background. Albuminuria is an early sign but not a strong predictor of diabetic kidney disease (DKD). Owing to their high stability, urinary exosomal miRNAs can be useful predictors of the progression of early-stage DKD to renal failure; fluid biopsies are ideal for detecting abnormalities in these miRNAs. The aim of this study was to identify novel differentially expressed miRNAs as urine biomarkers for type 2 DKD by comparing between patients of type 2 diabetes (T2D) with and without macroalbuminuria. Methods. Ten patients with T2D, including five who had no renal disease and five with macroalbuminuria (DKD G1-2A3), were selected for this study. Exosome- (UExo-) derived miRNA profiles were used to identify candidate biomarkers, a subset of which was verified using quantitative reverse transcription PCR. Results. A total of 496 UExo-derived miRNA species were found to be differentially expressed (>2-fold) in patients with DKD, compared to those with T2D. A validation analysis revealed that three miRNAs (miR-362-3p, miR-877-3p, and miR-150-5p) were upregulated and one (miR-15a-5p) was downregulated. These miRNAs might regulate DKD through p53, mTOR, and AMPK pathways. Conclusions. In conclusion, UExo-derived miRNAs were altered in type 2 DKD. MiR-362-3p, miR-877-3p, miR-150-5p, and miR-15a-5p might be novel biomarkers for incipient DKD.

scholarly journals Late Radiation–Related Toxicities in Patients Treated for Early-Stage Cervical Carcinoma by Surgery and Adjuvant Radiotherapy: A Retrospective Imaging Study

2021 ◽  
Vol 27 ◽  
Author(s):  
Katarina Nadova ◽  
Miroslava Burghardtova ◽  
Klara Fejfarova ◽  
Klaudia Reginacova ◽  
Hana Malikova
Keyword(s):  
Cervical Carcinoma ◽  
Adjuvant Radiotherapy ◽  
Early Stage ◽  
Clinical Manifestations ◽  
Inclusion Criteria ◽  
Imaging Results ◽  
The Mean ◽  
Risk Of Cancer ◽  
Tomography Scan

Surgical treatment is preferred therapy of early-stage cervical carcinoma. In the risk of cancer recurrence surgery is often followed by adjuvant radiotherapy. In our retrospective study we aimed at identifying late (≥6 months) and very late (≥5 years) radiation adverse effects on imaging scans as CT, PET/CT and MRI in patients who underwent successful treatment for cervical carcinoma by radical surgery combined with radiotherapy ± chemotherapy. We correlated imaging results with clinical manifestations. We selected young and middle-aged patients with long life expectancy, as late radiation-related toxicities may significantly affect their quality of life. Patients were selected from those who were primary diagnosed and treated between the years 1987–2011 and regularly visited our Oncology department in years 2011–2012. Following inclusion criteria were applied: age ≤55 years at diagnosis, clinical follow-up ≥5 years and at least one tomography scan ≥3 years after finished treatment. One hundred and three subjects were reviewed: 73 patients met all inclusion criteria, while 30 patients fulfilled the inclusion criteria except for available tomography scan ≥3 years after therapy. The mean imaging follow-up was 11.2 ± 7.6 years and the mean clinical follow-up was 15.0 ± 6.9 years. In 20 (27%) subjects 27 cases grade I radiation-related toxicities were found; 9 (33%) of those 27 cases were clinically silent. In 14 (19%) females only grade I toxicities were observed. Grade III-IV toxicities were found in 5 (6.8%) subjects. No grade V toxicities were observed. We concluded that severe late side effects caused by radiotherapy were exceedingly rare in females successfully treated for early-stage cervical carcinoma, only 1 bilateral osteonecrosis, 2 cases of ileus, and 2 potentially radiation-induced tumors were found. The majority of radiation-related comorbidities found on imaging scans were clinically silent.

scholarly journals Emerging Diabetic Novel Biomarkers of the 21st Century

2021 ◽  
Author(s):  
Shilpa Suneja ◽  
Sukanya Gangopadhyay ◽  
Vandana Saini ◽  
Rajni Dawar ◽  
Charanjeet Kaur
Keyword(s):  
21St Century ◽  
Early Stage ◽  
Continuous Process ◽  
Clinical Settings ◽  
The Novel ◽  
Lifestyle Management ◽  
Disease Condition ◽  
Novel Biomarkers

AbstractDiabetes is a growing epidemic with estimated prevalence of infected to reach ~592 million by the year 2035. An effective way to approach is to detect the disease at a very early stage to reduce the complications and improve lifestyle management. Although several traditional biomarkers including glucated hemoglobin, glucated albumin, fructosamine, and 1,5-anhydroglucitol have helped in ease of diagnosis, there is lack of sensitivity and specificity and are inaccurate in certain clinical settings. Thus, search for new and effective biomarkers is a continuous process with an aim of accurate and timely diagnosis. Several novel biomarkers have surged in the present century that are helpful in timely detection of the disease condition. Although it is accepted that a single biomarker will have its inherent limitations, combining several markers will help to identify individuals at high risk of developing prediabetes and eventually its progression to frank diabetes. This review describes the novel biomarkers of the 21st century, both in type 1 and type 2 diabetes mellitus, and their present potential for assessing risk stratification due to insulin resistance that will pave the way for improved clinical outcome.

scholarly journals Association between risk of type 2 diabetes and changes in energy intake at breakfast and dinner over 14 years: a latent class trajectory analysis from the China health and nutrition Survey, 1997–2011

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e046183
Author(s):  
Xiyun Ren ◽  
Jian Gao ◽  
Tianshu Han ◽  
Changhao Sun
Keyword(s):  
Type 2 Diabetes ◽  
Energy Consumption ◽  
Energy Intake ◽  
Latent Class ◽  
Early Stage ◽  
Harmful Effect ◽  
Nutrition Survey ◽  
Health And Nutrition ◽  
Diabetes Status

ObjectiveThis study aimed to investigate the association between the trajectories of energy consumption at dinner versus breakfast and the risk of type 2 diabetes (T2D).DesignCohort study.SettingThe study was conducted in China.ParticipantsA total of 10 727 adults, including 5239 men and 5488 women, with a mean age of 42.7±11.2 years and a mean follow-up time of 9.1 years, met the study criteria and completed a questionnaire about energy intake and diabetes status from the China Health and Nutrition Survey in 1997–2011.Primary outcome measuresParticipants were divided into subgroups based on the trajectories of the ratio of energy consumption at dinner versus breakfast. Cox multivariate regression models were used to explore the associations between different trajectories and the risk of T2D after adjustment for confounders and their risk factors. Mediation analysis was performed to explore the intermediary effect of triacylglycerol (TG), total cholesterol (TC), uric acid (UA) and apolipoprotein B (ApoB) between the trajectories and the risk of T2D.ResultsFor energy consumption at dinner versus breakfast, compared with a low-stable trajectory, the adjusted HR of T2D in low-increasing from early-stage trajectory was 1.29 (95% CI 1.04 to 1.60). TG, TC, UA and ApoB were significantly higher in low-increasing from early-stage trajectory than other trajectories and play partial regulation roles between trajectories and T2D.ConclusionsThis study emphasised the harmful effect of a gradual increase in the ratio of energy consumption at dinner versus breakfast from early stage on the development of T2D and partially mediated by TG, TC, UA and ApoB, highlighting that it is necessary to intake more energy at breakfast compared with dinner to prevent T2D in adults.

scholarly journals Plasma contact factors as novel biomarkers for diagnosing Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jung Eun Park ◽  
Do Sung Lim ◽  
Yeong Hee Cho ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Stage ◽  
Area Under The Curve ◽  
Contact System ◽  
Plasma Diagnostic ◽  
Vascular Abnormalities ◽  
Prodromal Ad ◽  
Novel Biomarkers

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia and most of AD patients suffer from vascular abnormalities and neuroinflammation. There is an urgent need to develop novel blood biomarkers capable of diagnosing Alzheimer’s disease (AD) at very early stage. This study was performed to find out new accurate plasma diagnostic biomarkers for AD by investigating a direct relationship between plasma contact system and AD. Methods A total 101 of human CSF and plasma samples from normal and AD patients were analyzed. The contact factor activities in plasma were measured with the corresponding specific peptide substrates. Results The activities of contact factors (FXIIa, FXIa, plasma kallikrein) and FXa clearly increased and statistically correlated as AD progresses. We present here, for the first time, the FXIIa cut-off scores to as: > 26.3 U/ml for prodromal AD [area under the curve (AUC) = 0.783, p < 0.001] and > 27.2 U/ml for AD dementia (AUC = 0.906, p < 0.001). We also describe the cut-off scores from the ratios of CSF Aβ1–42 versus the contact factors. Of these, the representative ratio cut-off scores of Aβ1–42/FXIIa were to be: < 33.8 for prodromal AD (AUC = 0.965, p < 0.001) and < 27.44 for AD dementia (AUC = 1.0, p < 0.001). Conclusion The activation of plasma contact system is closely associated with clinical stage of AD, and FXIIa activity as well as the cut-off scores of CSF Aβ1–42/FXIIa can be used as novel accurate diagnostic AD biomarkers.

scholarly journals Experts’ opinion on the detection and management of prediabetes in Lebanon

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110294
Author(s):  
Emile Andari ◽  
Paola Atallah ◽  
Sami Azar ◽  
Akram Echtay ◽  
Selim Jambart ◽  
...  
Keyword(s):  
Risk Factors ◽  
Preliminary Report ◽  
Early Stage ◽  
National Guidelines ◽  
Lifestyle Modifications ◽  
Multiple Tests ◽  
Lebanese Population ◽  
To Come ◽  
Near Future

Given that the complications of type 2 diabetes can start at an early stage, early detection and appropriate management of prediabetes are essential. We aimed to develop an expert opinion on prediabetes in Lebanon to pave the way for national guidelines tailored for the Lebanese population in the near future. A panel of seven diabetes experts conducted a thorough literature review and discussed their opinions and experiences before coming up with a set of preliminary recommendations for the detection and management of prediabetes in Lebanon. Lebanese physicians employ multiple tests for the diagnosis of prediabetes and no national cut-off values exist. The panel agreed that prediabetes screening should be focused on patients exceeding 45 years of age with otherwise no risk factors and on adults with risk factors. The panel reached that fasting plasma glucose (FPG) and HbA1c should be used for prediabetes diagnosis in Lebanon. FPG values of 100–125 mg/dL or HbA1c values of 5.7%–6.4% were agreed upon as indicative of prediabetes. For the management of prediabetes, a three-step approach constituting lifestyle modifications, pharmacological treatment and bariatric surgery is recommended. There should be more focus on research on prediabetes in Lebanon. This preliminary report will be further discussed with the Lebanese Society of Endocrinology, Diabetes and Lipids in 2021 in order to come up with the first Lebanese national guidelines for the detection and management of prediabetes in Lebanon.

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor

2007 ◽  
Vol 293 (2) ◽  
pp. R707-R713 ◽  
Author(s):  
Sharyn M. Fitzgerald ◽  
Barbara K. Kemp-Harper ◽  
Helena C. Parkington ◽  
Geoffrey A. Head ◽  
Roger G. Evans
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Arterial Pressure ◽  
Early Stage ◽  
Mesenteric Arteries ◽  
No Production ◽  
Wild Type ◽  
Early Diabetes ◽  
Diabetes In Mice ◽  
Vehicle Treatment

We determined whether nitric oxide (NO) counters the development of hypertension at the onset of diabetes in mice, whether this is dependent on endothelial NO synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 wk of Nω-nitro-l-arginine methyl ester (l-NAME; 100 mg·kg−1·day−1 in drinking water; 97 ± 3 mmHg) than after vehicle treatment (88 ± 3 mmHg). MAP was also elevated in eNOS null mice (113 ± 4 mmHg). Seven days after streptozotocin treatment (200 mg/kg iv) MAP was further increased in l-NAME-treated mice (108 ± 5 mmHg) but not in vehicle-treated mice (88 ± 3 mmHg) nor eNOS null mice (104 ± 3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic l-NAME or induction of diabetes but was reduced by 42 ± 6% in l-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by l-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries, diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production.

scholarly journals Targeting the Incretin/Glucagon System With Triagonists to Treat Diabetes

2018 ◽  
Vol 39 (5) ◽  
pp. 719-738 ◽  
Author(s):  
Megan E Capozzi ◽  
Richard D DiMarchi ◽  
Matthias H Tschöp ◽  
Brian Finan ◽  
Jonathan E Campbell
Keyword(s):  
Metabolic Disease ◽  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Drug Class ◽  
Clinical Findings ◽  
Metabolic Dysfunction ◽  
Multiple Receptors ◽  
Insulinotropic Peptide ◽  
The Brain

Abstract Glucagonlike peptide 1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of glucagonlike peptide 1 receptor–directed strategies is submaximal, and the only potent, sustainable treatment of metabolic dysfunction is bariatric surgery, necessitating the development of unique therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors. In this review, we discuss the range of tissue targets and added benefits afforded by the inclusion of each of GIP and glucagon. We discuss considerations for the development of sequence-intermixed dual agonists and triagonists, highlighting the importance of evaluating balanced signaling at the targeted receptors. Several multireceptor agonist peptides have been developed and evaluated, and the key preclinical and clinical findings are reviewed in detail. The biological activity of these multireceptor agonists are founded in the success of GLP-1-directed strategies; by including GIP and glucagon components, these multireceptor agonists are thought to enhance GLP-1’s activities by broadening the tissue targets and synergizing at tissues that express multiple receptors, such at the brain and pancreatic isletβ cells. The development and utility of balanced, unimolecular multireceptor agonists provide both a useful tool for querying the actions of incretins and glucagon during metabolic disease and a unique drug class to treat type 2 diabetes with unprecedented efficacy.

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