Plasma miR-126 Is a Potential Biomarker for Early Prediction of Type 2 Diabetes Mellitus in Susceptible Individuals

Type 2 diabetes mellitus (T2DM) is a major public health problem in China. Diagnostic markers are urgently needed to identify individuals at risk of developing T2DM and encourage them to adapt to a healthier life style. Circulating miRNAs present important sources of noninvasive biomarkers of various diseases. Recently, a novel plasma microRNA signature was identified in T2DM. Here, we evaluated the T2DM-related miRNA signature in plasma of three study groups: normal (fasting glucose (FG), 4.8–5.2 mmol/L), T2DM-susceptible (FG, 6.1–6.9 mmol/L), and T2DM individuals (FG, ≥7.0 mmol/L) and tested the feasibility of using circulating miRNAs to identify individuals at risk of developing T2DM. Among the 5 miRNAs included in the signature, miR-29b and miR-28-3p are not detectable. miR-15a and miR-223 have comparable expression levels among three groups. Notably, miR-126 is the only miRNA that showed significantly reduced expression in susceptible individuals and T2DM patients compared to normal individuals, suggesting that miR-126 in circulation may serve as a potential biomarker for early identification of susceptible individuals to T2DM.

Download Full-text

GDF-15 and neutrophils in patients with heart failure and type 2 diabetes mellitus

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.028 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

AA Garganeeva ◽

EA Kuzheleva ◽

VA Fedyunina ◽

VA Aleksandrenko

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Inflammatory Marker ◽

Study Groups ◽

Significant Negative Correlation ◽

Enzyme Linked Immunosorbent Assay ◽

National Budget

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was funded by (subject of fundamental scientific research on a state assignment № АААА-А17-117052310073-6 от 23.05.2017 Introduction. Growth differentiation factor-15 (GDF-15) is a biomarker associated with inflammatory processes in the pathogenesis of chronic heart failure (CHF) which expresses in cardiomyocytes under pathological conditions. The relationship between the level of GDF-15 and type 2 diabetes mellitus (T2DM) has also been proven. It is necessary to study GDF-15 in patients with CHF and T2DM. Aim To investigate the association between serum GDF-15 levels in patients with CHF of ischemic etiology and the concentration of the main leukocyte fractions depending on presence or absence of T2DM. Material and methods. The study included 42 patients. The patients were divided into 2 groups. The first group consisted of patients with CHF and T2DM (n = 14). The second group consisted of patients with CHF without T2DM (n = 28). Determination of GDF-15 concentration was carried out by enzyme-linked immunosorbent assay (BioVendor, Czech Republic). The absolute concentration of lymphocytes, neutrophils, as well as the ratio of neutrophils to lymphocytes in the blood were analyzed. Statistical analysis was performed using the Statistica software (v.10.0). The data were described as a median and interquartile range, the Mann-Whitney test was used to compare them. The correlation analysis was tested using the Spearman"s correlation coefficient. Results and discussion. The average level of the GDF-15 in the study groups was comparable: 2389 (2104; 3375) pg/ml and 2309 (2047; 3014) pg/ml in the first and second groups, respectively (p = 0.6). In the general cohort of CHF patients, the GDF-15 concentration was not correlate with the lymphocytes concentration (r = -0.001, p = 0.95), neutrophils (r = -0.14, p = 0.4) and the ratio of neutrophils to lymphocytes (r = -0.12, p = 0.25). At the same time, in the group of patients with T2DM, a significant negative correlation was revealed between the concentration of GDF-15 in the serum and the concentration of neutrophils (r = -0.6, p = 0.022). While both other analyzed parameters did not demonstrate significant correlations with GDF-15 (p > 0.05). In the group of CHF patients without T2DM, no correlations were found between GDF-15 and the studied parameters, including neutrophils (r = 0.02, p = 0.3). Along with this the median of the neutrophils concentration did not vary among groups (3.5 (2.3; 5.3) vs 3.2 (2.7; 4.1) * 109 / l; p = 0.8). Conclusion The concentration of the inflammatory marker GDF-15 in the blood of patients with CHF in combination with T2DM correlates with the concentration of neutrophils. In the absence of T2DM, no significant correlations were found between GDF-15 and the main leukocyte fractions. The results obtained indicate the possible prospect of using the GDF-15 biomarker in a cohort of patients with CHF in combination with T2DM.

Download Full-text

Circulating miRNAs as Predictive Biomarkers of Type 2 Diabetes Mellitus Development in Coronary Heart Disease Patients from the CORDIOPREV Study

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2018.05.002 ◽

2018 ◽

Vol 12 ◽

pp. 146-157 ◽

Cited By ~ 25

Author(s):

Rosa Jiménez-Lucena ◽

Oriol Alberto Rangel-Zúñiga ◽

Juan Francisco Alcalá-Díaz ◽

Javier López-Moreno ◽

Irene Roncero-Ramos ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Coronary Heart Disease ◽

Type 2 Diabetes Mellitus ◽

Heart Disease ◽

Predictive Biomarkers ◽

Circulating Mirnas

Download Full-text

How does specific advice to increase exercise or advice to both increase exercise and improve diet affect outcomes in people at risk of developing type 2 diabetes mellitus?

Cochrane Clinical Answers ◽

10.1002/cca.60 ◽

2016 ◽

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

At Risk ◽

Type 2 Diabetes Mellitus ◽

Specific Advice

Download Full-text

Evaluating the impact of type 2 diabetes mellitus on CYP450 metabolic activities: protocol for a case–control pharmacokinetic study

BMJ Open ◽

10.1136/bmjopen-2017-020922 ◽

2018 ◽

Vol 8 (2) ◽

pp. e020922 ◽

Cited By ~ 2

Author(s):

Sophie Gravel ◽

Jean-Louis Chiasson ◽

Suzanne Dallaire ◽

Jacques Turgeon ◽

Veronique Michaud

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Adult Population ◽

Study Groups ◽

Primary Objective ◽

Research Centre ◽

Probe Drug ◽

The Impact

IntroductionDiabetes affects more than 9% of the adult population worldwide. Patients with type 2 diabetes mellitus (T2DM) show variable responses to some drugs which may be due, in part, to variability in the functional activity of drug-metabolising enzymes including cytochromes P450 (CYP450s). CYP450 is a superfamily of enzymes responsible for xenobiotic metabolism. Knowledge must be gained on the impact of T2DM and related inflammatory processes on drug metabolism and its consequences on drug response. The aim of this study is to characterise the activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4/5 in T2DM versus non-T2DM subjects following the administration of a cocktail of probe drug substrates.Methods and analysisThis single-centre clinical study proposes the first detailed characterisation of T2DM impacts on major CYP450 drug-metabolising enzyme activities. We intend to recruit 42 patients with controlled T2DM (A1C≤7%), 42 patients with uncontrolled T2DM (A1C>7%) and 42 non-diabetic control subjects. The primary objective is to determine and compare major CYP450 activities in patients with T2DM versus non-diabetic subjects by dosing in plasma and urine probe drug substrates and metabolites following the oral administration of a drug cocktail: caffeine (CYP1A2), bupropion (CYP2B6), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4/5). Secondary objectives will evaluate the influence of variables such as glycaemia, insulinaemia, genetic polymorphisms and inflammation. The value of an endogenous biomarker of CYP3A activity is also evaluated. The first patient was recruited in May 2015 and patients will be enrolled up to completion of study groups.Ethics and disseminationApproval was obtained from the ethic review board of the CHUM research centre (Montreal, Canada).Trial registration numberNCT02291666.

Download Full-text

Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302009000200008 ◽

2009 ◽

Vol 53 (2) ◽

pp. 165-174 ◽

Cited By ~ 22

Author(s):

Hala Tfayli ◽

Silva Arslanian

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Beta Cell ◽

Polycystic Ovary ◽

Significant Proportion ◽

Public Health Problem ◽

Family History Of Diabetes ◽

Beta Cell Failure

Type 2 diabetes mellitus (T2DM) in children and adolescents is an important Public Health problem against the backdrop of the epidemic of childhood obesity. The clinical presentation of T2DM in youth is heterogeneous from minimal symptomatology to diabetic ketoacidosis. The increasing rates of youth T2DM have paralleled the escalating rates of obesity, which is the major risk factor impacting insulin sensitivity. Additional risk factors include minority race, family history of diabetes mellitus, maternal diabetes during pregnancy, pubertal age group and conditions associated with insulin resistance (IR) - such as polycystic ovary syndrome (PCOS). The pathophysiology of T2DM has been studied extensively in adults, and it is widely accepted that IR together with beta-cell failure are necessary for the development of clinical diabetes mellitus in adulthood. However, pathophysiologic studies in youth are limited and in some cases conflicting. Similar to adults, IR is a prerequisite, but beta-cell failure is necessary for progression from normal glucose tolerance to prediabetes and frank diabetes in youth. Even though rates of T2DM in youth are increasing, the overall prevalence remains low if compared with type 1 diabetes mellitus (T1DM). However, as youth with T1DM are becoming obese, the clinical distinction between T2DM and obese T1DM has become difficult, because of the overlapping clinical picture with evidence of islet cell autoimmunity in a significant proportion of clinically diagnosed youth with T2DM. The latter are most likely obese children with autoimmune T1DM who carry a misdiagnosis of T2DM. Further research is needed to probe the pathophysiological, immunological, and metabolic differences between these two groups in the hopes of assigning appropriate therapeutic regimens. These challenges combined with the evolving picture of youth T2DM and its future complications provide unending opportunities for acquisition of new knowledge in the field of childhood diabetes.

Download Full-text

Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for development of type 2 diabetes mellitus

10.1002/14651858.cd012106 ◽

2016 ◽

Author(s):

Bianca Hemmingsen ◽

Jesper Krogh ◽

Maria-Inti Metzendorf ◽

Bernd Richter

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

At Risk ◽

Type 2 Diabetes Mellitus ◽

Sodium Glucose Cotransporter

Download Full-text

Effects of substituting eggs for high-carbohydrate breakfast foods on the cardiometabolic risk-factor profile in adults at risk for type 2 diabetes mellitus

European Journal of Clinical Nutrition ◽

10.1038/s41430-020-0599-2 ◽

2020 ◽

Vol 74 (5) ◽

pp. 784-795

Author(s):

Kevin C. Maki ◽

Orsolya M. Palacios ◽

Melvyn W. Kramer ◽

Rupal Trivedi ◽

Mary R. Dicklin ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

At Risk ◽

Type 2 Diabetes Mellitus ◽

Risk Factor ◽

Cardiometabolic Risk ◽

Cardiometabolic Risk Factor ◽

Risk Factor Profile ◽

High Carbohydrate

Download Full-text

Determinants of Increased Serum Calprotectin in Patients with Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms21218075 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8075

Author(s):

Milou M. Oosterwijk ◽

Stephan J.L. Bakker ◽

Tom Nilsen ◽

Gerjan Navis ◽

Gozewijn D. Laverman

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Vascular Inflammation ◽

Strong Association ◽

Median Serum ◽

Potential Biomarker ◽

Calprotectin Level ◽

Peripheral Artery Diseases

Circulating calprotectin is a potential biomarker for endovascular inflammation in type 2 diabetes mellitus (T2DM). We investigated the determinants of calprotectin and its relationship with the presence of cardiovascular disease (CVD) in 362 T2DM patients included in the Diabetes and Lifestyle Cohort Twente-1 (DIALECT-1) study. Lifestyle exposures, including nutrition, were determined by validated questionnaires. CVD was defined as coronary artery diseases, strokes, and peripheral artery diseases. Median serum calprotectin levels were 1.04 mg/L [IQR: 0.73–1.46 mg/L] and were higher in women (1.11 mg/L) than men (0.96 mg/L, p = 0.007). Current smoking was a major independent determinant of circulating calprotectin, with a 51% higher calprotectin compared to never smoking (p < 0.001). Albuminuria (p = 0.011), former smoking (p = 0.023), and intake of mono- and disaccharides (p = 0.005) also contributed independently to circulating calprotectin. Each incremental increase in calprotectin level was associated with 1.36-times higher odds for CVD (95% CI 1.04–1.77, p = 0.026). In the current study, calprotectin was the only inflammatory parameter significantly associated with CVD. The strong association of circulating calprotectin with smoking, a well-known direct cause of vascular inflammation, and also with CVD, stresses the urge for further research to define its role as a biomarker in T2DM.

Download Full-text